From activation to desensitization: How ABA balances plant growth and abiotic stress response?

Abstract

Abscisic acid (ABA) signaling is a central regulator of plant adaptation to abiotic stress, dynamically coordinating stress responses with growth and development. Rapid activation of ABA signaling promotes plant survival during the early stages of stress, whereas prolonged stress requires timely attenuation of the pathway to restore growth and prevent excessive stress responses. Recent studies have uncovered diverse mechanisms underlying ABA desensitization, including regulation of SnRK2 kinases, phytohormone crosstalk, nutrient signaling, protein trafficking, post-translational modifications, and feedback regulatory networks. Together, these interconnected mechanisms enable plants to fine-tune ABA signaling in response to developmental and environmental cues. In this review, we summarize recent advances in understanding the molecular mechanisms that attenuate ABA signaling and restore the balance between growth and stress adaptation during prolonged stress. We also highlight outstanding questions and discuss strategies for engineering ABA signaling dynamics to improve crop resilience, productivity, and adaptation to increasingly variable environments.

The dynamic regulation of ABA signaling provides critical insights into how plants balance growth and abiotic stress responses under fluctuating environmental conditions. This manuscript reviews recent advances in the molecular mechanisms governing the activation and desensitization of ABA signaling, highlighting the coordinated roles of SnRK2 kinases, phytohormone and nutrient signaling pathways, protein trafficking, and feedback regulation in shaping ABA signaling dynamics and optimizing the growth–stress balance.

Introduction

Plants are continually challenged by abiotic stresses, such as drought, salinity, and heavy metal toxicity, whose onset, duration, and intensity are often unpredictable (Zhang et al., 2022, 2025b; Nawaz et al., 2023). These environmental constraints can be broadly classified as short-term or prolonged, depending on their duration (Wang et al., 2023; Lu et al., 2024). Short-term stresses, although temporary, can trigger rapid physiological and molecular responses, enabling acclimation and promoting survival. By contrast, prolonged exposure to adverse conditions can severely disrupt cellular homeostasis, impair metabolic processes, and compromise plant growth. Abscisic acid (ABA) is a central phytohormone that regulates plant development and responses to abiotic stresses, including drought, osmotic stress, and salt stress (Kavi Kishor et al., 2022; Luo et al., 2022, 2024; Yang et al., 2023; Li et al., 2025a; Ma et al., 2025; Yuan and Zhao, 2025). Accordingly, rapid activation and timely attenuation of ABA signaling are critical for survival under fluctuating stress conditions. Transient activation of ABA signaling enhances stress tolerance by modulating stomatal closure, osmotic adjustment, and the expression of stress-responsive genes. However, sustained or excessive ABA signaling inhibits cell division, growth, and photosynthesis, ultimately reducing plant fitness (Lu et al., 2024). Thus, precise modulation of ABA signaling is required to balance stress tolerance with growth and development, particularly under prolonged or recurrent stress conditions. Elucidating the molecular mechanisms that control the dynamics of ABA perception, signal transduction, and feedback regulation could thus provide a mechanistic basis for improving stress resilience.

The core ABA signaling module has been extensively characterized under short-term stress conditions. It comprises the ABA receptors pyrabactin resistance 1 (PYR1)/PYR1-LIKE (PYL)/regulatory component of ABA receptors (RCAR), clade A protein phosphatases 2C (PP2Cs), and sucrose non-fermenting 1-related protein kinases 2 (SnRK2s) (Huang et al., 2024). Recent studies have further expanded this model by demonstrating that the nitrate transporter/receptor NRT1.1B directly participates in ABA perception at the plasma membrane (Ma et al., 2025). By contrast, the mechanisms that desensitize ABA signaling during prolonged stress have only recently begun to be elucidated (Wang et al., 2023; Lu et al., 2024). Emerging evidence suggests that ABA desensitization involves a highly integrated regulatory network that includes feedback regulation of SnRK2 kinase abundance and subcellular distribution and SnRK2-catalyzed phosphorylation of glucose-6-phosphate/phosphate translocator 1 (GPT1), which together dynamically modulate ABA signaling over time (Lu et al., 2024). Furthermore, extensive crosstalk with growth-promoting pathways and other phytohormone signaling networks enables plants to integrate environmental and developmental cues, thereby optimizing resource allocation under sustained stress conditions (Yang et al., 2014). Dissecting how these signaling interactions change across different stress durations will be essential for designing targeted interventions and may ultimately guide strategies for improving crop stress tolerance.

This review focuses on recent advances in our understanding of ABA-mediated stress responses, with particular attention to the mechanisms by which ABA signaling modulates the balance between stress tolerance and growth under prolonged stress conditions. Specifically, we examine the regulatory processes that drive ABA desensitization during prolonged stress. Finally, we highlight recent findings, identify outstanding questions, and discuss the implications of these insights for improving crop resilience while minimizing growth penalties.

ABA: The master regulator of plant stress responses and development

Abiotic stress induces ABA biosynthesis, and ABA subsequently modulates diverse physiological processes involved in stress adaptation and plant development. In the absence of ABA, PP2Cs inhibit SnRK2 kinases by dephosphorylating them, thereby maintaining the pathway in an inactive state. Under stress conditions, however, ABA levels rise, and ABA is perceived by PYR/PYL/RCAR receptors. ABA binding promotes the formation of receptor–PP2C complexes, leading to the inhibition of PP2C activity. This inhibition allows SnRK2s to undergo autophosphorylation, rendering them fully active (Huang et al., 2024). Once activated, SnRK2s phosphorylate various targets, including ion channels, metabolic enzymes, and transcription factors, which mediate rapid physiological responses and stress-induced changes in gene expression (Ayub et al., 2025; Wei et al., 2025).

For example, in rice (Oryza sativa), the MADS-box transcription factor OsMADS23 enhances responses to drought and salinity by promoting the expression of ABA biosynthesis genes, such as nine-cis-epoxycarotenoid dioxygenase 2 (OsNCED2), OsNCED3, and OsNCED4, resulting in increased ABA accumulation (Li et al., 2021). In addition, SnRK-type protein kinases, such as stress-activated protein kinase 9 (SAPK9), physically interact with OsMADS23, enhancing its stability and activity in an ABA-dependent manner (Li et al., 2021). Elevated ABA levels induced by stress also trigger changes in the expression of numerous factors that help plants respond to and withstand adverse conditions (Pardo-Hernández et al., 2024; Zhou et al., 2024; Ma et al., 2025; Wan et al., 2025). These factors include, among others, ethylene-responsive factor 19 (ERF19) (Huang et al., 2021), XPO1-interacting WD40 protein 1 (XIW1) (Xu et al., 2019), and ABRE-binding factors (AREB/ABF) (Ayub et al., 2025).

In Arabidopsis, XIW1 positively regulates ABA signaling (Xu et al., 2019). The loss-of-function mutant xiw1 exhibits an ABA-insensitive phenotype, and under ABA treatment, shows lower levels of the transcription factor ABI5 than wild-type plants (Xu et al., 2019). XIW1 accumulates in the nucleus under stress conditions, where it interacts with and stabilizes ABI5, thereby enhancing ABA signaling (Xu et al., 2019). Overexpression of XIW1 has been shown to improve drought tolerance in plants (Xu et al., 2019), underscoring its potential application in agricultural biotechnology. ABA signaling also promotes stomatal closure by regulating anion channels and turgor pressure, thereby reducing transpirational water loss (Bharath et al., 2021). In the nucleus, activated SnRK2s promote the transcription of stress-responsive genes by phosphorylating transcription factors such as AREB/ABF, which bind to ABA-responsive elements (ABREs) in the promoters of downstream genes (Joo et al., 2021; Lin et al., 2021). Extensive post-translational modifications (PTMs), including phosphorylation, ubiquitination, and SUMOylation, further strengthen plant stress responses (Joo et al., 2021; Lin et al., 2021; Hao et al., 2026). In addition, N6-methyladenosine (m⁶A) mRNA modification and its reader, the evolutionarily conserved C-terminal region 8 (ECT8), establish an important negative feedback checkpoint for ABA signaling (Wu et al., 2024). Upon ABA treatment, this system facilitates the sequestration of the m⁶A-modified transcript of the ABA receptor gene pyrabactin resistance 1-like 7 (PYL7) into liquid-liquid phase-separated ECT8 condensates located within stress granules (Wu et al., 2024). This process establishes a feedback mechanism that helps prevent excessive stress responses and maintain basal growth. In addition to RNA modifications, histone modifications are also involved in ABA-mediated plant growth and stress responses (Chen et al., 2020; Li et al., 2025b). The expression of CYP707A, which encodes a key enzyme involved in ABA catabolism, is regulated by the histone modification H3K27me3. The H3K27me3 demethylase relative of early flowering 6 (REF6) promotes ABA metabolism and thereby reduces seed dormancy in Arabidopsis (Chen et al., 2020). Using CRISPR–Cas9 technology to disrupt the binding of REF6 to the CTCTGYTY motif within an intron of CYP707A successfully reduced CYP707A expression in wheat (Li et al., 2025b). This reduction led to increased ABA levels and drought resistance while maintaining yield. Overall, the intricate network of ABA signaling pathways not only enhances plant resilience to abiotic stress but also highlights the importance of precise regulatory mechanisms in maintaining physiological homeostasis.

Activation and termination of ABA signaling

ABA reprograms transcriptional dynamics and modulates the biosynthesis, PTMs, and functional activity of various proteins, thereby influencing plant stress responses that are vital for survival under adverse environmental conditions. However, sustained activation of ABA signaling can induce excessive responses, adversely affecting plant growth and post-stress recovery. Consequently, effective termination of ABA signaling is as critical as its initiation for maintaining appropriate physiological responses. Precise regulation of ABA signaling is therefore essential for plant adaptation to fluctuating environmental conditions.

Central roles of SnRK2s in activating and amplifying ABA signaling

Central to the ABA regulatory network are SnRK2 kinases, which function as key integrators of growth and stress signaling pathways (Hasan et al., 2022). Under optimal conditions with low ABA concentrations, SnRK2s promote vegetative growth and biomass accumulation (Shin et al., 2007; Zheng et al., 2010). By contrast, under stress conditions characterized by elevated ABA levels, these kinases inhibit growth as part of the adaptive response (Hasan et al., 2022). PTMs further fine-tune the activity, stability, subcellular localization, and protein–protein interactions of SnRK2s (Hu et al., 2024; Lu et al., 2024). As a result, SnRK2 proteins fulfill a bifunctional role by activating stress response pathways while also controlling plant growth and development.

The SnRK2 family displays substantial functional redundancy, such that pronounced hypersensitivity-to-stress phenotypes are generally observed only in higher-order snrk2 mutants (Fujii and Zhu, 2009; Fujii et al., 2011). Mechanistically, under osmotic stress or upon exogenous ABA application, subgroup I SnRK2s (SnRK2.1/4/5/9/10) undergo stress-induced liquid–liquid phase separation, leading to the formation of cytosolic biomolecular condensates (Yuan and Zhao, 2025). This phase separation spatially segregates the kinases from their negative regulators, notably clade A PP2Cs such as ABA-INSENSITIVE 1 (ABI1), thereby relieving PP2C-mediated inhibition and promoting the activation of subgroup I SnRK2s (Yuan and Zhao, 2025).

Osmotic stress rapidly activates a subset of Raf-like protein kinases (RAFs), which in turn phosphorylate and activate SnRK2s (Lin et al., 2020; Soma et al., 2020; Takahashi et al., 2020). Reversible phosphorylation is central to the regulation of SnRK2s; dephosphorylated SnRK2.6 and SnRK2.4 are incapable of self-activation, rendering RAF-mediated transphosphorylation essential for their activation (Lin et al., 2021). The B2/B3 and B4 RAFs are alternatively designated osmotic stress-activated protein kinase-100 kDa (OK¹⁰⁰) and -130 kDa (OK¹³⁰), respectively (Lin et al., 2020; Lozano-Juste et al., 2020). Similar to the snrk2.2/3/6 triple mutant, the OK¹⁰⁰-oct (raf3, 4, 5, 7, 8, 9, 10, 11) and OK¹⁰⁰-nonu (raf3, 4, 5, 6, 7, 8, 9, 10, 11) high-order mutants exhibit reduced ABA sensitivity during seed germination (Lin et al., 2021). In the OK¹⁰⁰-nonu mutant, ABA-induced activation of SnRK2s is compromised, demonstrating that B2/B3 RAFs are integral components of the ABA signaling pathway. Following their initial activation by RAFs, SnRK2s can additionally trans-phosphorylate inactive SnRK2 molecules in an intermolecular manner, thereby amplifying the stress response (Lin et al., 2021). Collectively, these findings support a model in which the RAF-SnRK2 kinase module is required for both the initiation and amplification of stress signaling.

Among SnRK family members, SnRK2.2, SnRK2.3, and SnRK2.6 are strongly induced by ABA, thereby activating adaptive responses and regulating downstream gene expression (Soma et al., 2023; Li et al., 2025a; Yuan and Zhao, 2025). Consistent with their positive regulatory role in ABA signaling, the snrk2.2/3/6 triple mutant displays enhanced seed germination and seedling growth in the presence of high concentrations of ABA (Fujii and Zhu, 2009). Conversely, overexpression of SnRK2.6 or SnRK2.8 results in ABA hypersensitivity, manifested as reduced seed germination and shortened hypocotyls and primary roots (Shin et al., 2007; Zheng et al., 2010). SnRK2s also regulate root gravitropism by phosphorylating the auxin transporter PIN2 at S259. In addition, the AGCVIII kinase pinoid (PID) phosphorylates PIN2 at S258. Phosphorylation of S259 by SnRK2 interferes with the ability of PID to phosphorylate S258 because of steric constraints (Sheng et al., 2025). This indicates that, under normal conditions, dominant regulation by PID ensures vertical root growth. Under adverse conditions, however, activated SnRK2 alters PIN2 function by antagonizing PID, causing roots to grow at an angle to avoid stress (Sheng et al., 2025). Furthermore, drought-induced ABA activates SnRK2.6, which phosphorylates ABI5 and promotes the expression of drought-responsive genes. Concurrently, SnRK2.6 phosphorylates and stabilizes proteasome regulator 1 (PTRE1), which increases proteasome activity and thereby promotes ABI5 degradation (Hao et al., 2026). This mechanism ensures a rapid response to drought while preventing excessive growth inhibition. Thus, the desensitization and eventual termination of ABA signaling are essential for survival under prolonged stress conditions. Mechanisms that attenuate or terminate ABA signaling include SnRK2 relocalization, protein degradation, PTMs, and feedback regulation.

Mechanisms underlying the termination of ABA signaling

A WD40-repeat protein in Arabidopsis, designated ABA TERMINATOR (ABT), has been identified as a key regulator of ABA signaling termination during seed germination and seedling establishment (Wang et al., 2020). Loss-of-function abt mutants display hypersensitivity to ABA in both germination and cotyledon greening assays, whereas plants overexpressing ABT show reduced sensitivity to ABA (Wang et al., 2020). Both in vivo and in vitro analyses demonstrated that ABT interacts with multiple ABA receptors of the PYR1/PYL family, as well as with co-receptor PP2C proteins (e.g., ABI1). ABT binds to the interaction sites of ABA receptors and the co-receptor ABI1, thereby competitively disrupting the formation of the PYR1/PYL–ABI1 receptor–co-receptor complex (Wang et al., 2020). Importantly, the binding affinity of ABT for ABI1 is significantly higher than that of PYR1 for ABI1, indicating that, when ABT is present, ABI1 preferentially associates with ABT rather than with ABA receptors. This preferential association reduces the ability of PYR1/PYLs to bind and inhibit ABI1, thereby strengthening ABI1-mediated negative regulation of ABA signaling (Wang et al., 2020). ABT expression is strongly induced by ABA, indicating that ABT functions in a negative feedback loop to attenuate ABA signaling after pathway activation (Wang et al., 2020).

Moreover, Arabidopsis EL1-like (AEL) proteins, a family of casein kinases involved in the regulation of diverse physiological processes, phosphorylate PYR/PYL proteins, thereby promoting their ubiquitination and subsequent degradation, which in turn attenuates ABA responses (Chen et al., 2018). Consistent with this role, the ael123/124/134 triple mutant exhibits hypersensitivity to ABA, which correlates with reduced degradation and consequent accumulation of PYR/PYL proteins. Furthermore, mutations in conserved AEL-mediated phosphorylation sites on PYR/PYL proteins lead to decreased phosphorylation, ubiquitination, and degradation, ultimately enhancing ABA sensitivity (Chen et al., 2018). Collectively, these findings indicate that dynamic interactions between ABT and ABA receptors, together with the post-translational regulation of PYR/PYL receptors, constitute a sophisticated regulatory mechanism that ensures the precise termination of ABA signaling in response to environmental cues.

SnRK2 homologs have been extensively characterized in major crop species, including rice, maize (Zea mays), and wheat (Triticum aestivum), and have been validated as crucial regulators of abiotic stress responses, including responses to drought, salinity, and low temperatures (Zhong et al., 2020; Du et al., 2024; Zhang et al., 2025c). From a breeding perspective, it is important to identify favorable alleles that enhance the activity of the RAF–SnRK2 signaling cascade within crop germplasm and to incorporate these alleles into elite varieties using molecular breeding approaches. Nonetheless, because of functional redundancy within the SnRK2 gene family and the complexity of the RAF–SnRK2 regulatory network, the contribution of a single gene is likely to be limited. Future crop improvement efforts should therefore prioritize the coordinated manipulation of multiple beneficial loci, including the simultaneous optimization of RAF and SnRK2 activities, together with the fine-tuning of ABA signal activation and termination, to achieve a balanced trade-off between stress tolerance and growth.

ABA-mediated balance between growth and stress responses

Under stress, ABA levels increase rapidly, suppressing plant growth while simultaneously enhancing stress tolerance. Once the stress subsides, ABA levels decrease, facilitating the resumption of growth. However, the duration and intensity of stress that plants encounter can be unpredictable. Therefore, plants must balance stress responses with developmental processes, particularly under prolonged stress conditions (Li et al., 2019). Recent studies have highlighted various molecular mechanisms that regulate ABA-mediated stress responses and plant growth. These mechanisms include phytohormone homeostasis (Yang et al., 2014), hormonal crosstalk (Xie et al., 2024), nutrient–hormone interactions (Ma et al., 2025b), and key regulators such as target of rapamycin (TOR) and SnRK2s, all of which contribute to balancing stress tolerance and growth. This dynamic regulation promotes plant survival under fluctuating environmental conditions while optimizing post-stress growth recovery.

Phytohormone homeostasis balances growth and stress tolerance

Prolonged ABA exposure drives widespread shifts in phytohormone biosynthesis and signaling (Yang et al., 2014). During prolonged ABA exposure, gibberellin (GA)- and cytokinin-associated signaling pathways are notably suppressed, whereas pathways associated with auxin and brassinosteroids are reactivated (Yang et al., 2014). The alleviation of brassinosteroid inhibition, together with the sustained promotion of auxin signaling, likely facilitates basal growth (Yang et al., 2014). These findings indicate that the regulation of phytohormone levels is critical for maintaining both plant growth and effective stress responses. They also raise the possibility that the exogenous application of specific phytohormones could enhance stress tolerance in agricultural production. Further investigation of the complex interactions among phytohormones may reveal novel regulatory pathways in crops.

Homeostasis between ABA and indole-3-acetic acid (IAA) is important for maintaining the balance between plant growth and stress responses (Teng et al., 2022). Tryptophan synthase β-subunit 1 (TSB1) is essential for maintaining auxin and ABA homeostasis. TSB1 facilitates tryptophan biosynthesis, which influences IAA concentration and contributes to plant stress tolerance (Yuan et al., 2017; Liu et al., 2022b). Compared with the wild type, both the amiR-TSB1 line and the trp2 mutant exhibit stunted growth, which is associated with elevated ABA levels and enhanced tolerance to drought and salt stress (Liu et al., 2022b). Mechanistically, TSB1 interacts with β-glucosidase 1 (BG1), an enzyme that catalyzes the hydrolysis of inactive ABA glucosyl ester (ABA-GE) to release active ABA. This interaction negatively regulates BG1 activity, thereby reducing ABA accumulation (Liu et al., 2022b). Concurrently, drought and salt stress induce hydrogen peroxide (H₂O₂) production, which promotes the sulfenylation of TSB1 (Liu et al., 2022b). This modification inhibits TSB1 enzymatic activity, thereby reducing tryptophan and IAA levels, and also disrupts the interaction between TSB1 and BG1, thereby promoting ABA accumulation and enhancing stress tolerance (Liu et al., 2022b). These findings underscore the critical role of homeostasis between ABA and IAA in maintaining a balance between growth and stress responses (Figure 1A).

Figure 1.

Proposed networks through which ABA balances plant growth and stress responses.

(A) Under optimal conditions, TSB1 enhances the synthesis of Trp and IAA, thereby promoting plant growth while simultaneously inhibiting BG1 to limit ABA accumulation. When plants are exposed to salt or drought stress, TSB1 expression is downregulated, leading to reduced Trp and auxin production. This reduction suppresses growth while relieving the inhibitory effect of TSB1 on BG1, thereby promoting ABA accumulation and enhancing stress tolerance. In addition, H₂O₂-dependent sulfenylation of TSB1 under these stress conditions disrupts its interaction with BG1, further increasing ABA levels. TOR phosphorylates PYLs to attenuate stress responses under non-stress conditions. By contrast, during stress, SnRK2s phosphorylate RAPTOR, inhibiting TOR activity and repressing growth.

(B) Under conditions characterized by high GA and low ABA levels, GA-induced degradation of SLR1 releases OsNAC120, which activates GA biosynthetic genes while repressing genes involved in ABA biosynthesis, thereby promoting GA-driven growth. Under drought stress, ABA-activated OsSAPK9 phosphorylates OsNAC120 and promotes its degradation, while stress-induced SLR1 further reduces OsNAC120 transcriptional activity, shifting the balance from growth toward stress responses.

(C) Under low-nitrate conditions, ABA enhances the interaction between NRT1.1B and SPX4, promoting the release of NLP4 and its translocation into the nucleus, where it activates ABA-responsive pathways. Under high-nitrate conditions, nitrate competes with ABA for binding to NRT1.1B, shifting NRT1.1B activity toward nitrate sensing. Arrow thickness indicates the strength of the signal or regulatory effect: thicker arrows represent stronger effects, whereas thinner arrows represent weaker effects.

S, sulfenylation; P, phosphorylation; U, ubiquitination.

In addition, antagonism between GA and ABA plays a key role in regulating the balance between stress responses and growth (Xie et al., 2024). In this regulatory network, OsNAC120 functions as a context-dependent transcriptional hub (Xie et al., 2024). Under non-stress conditions, characterized by elevated GA levels and reduced ABA levels, GA-induced degradation of the DELLA repressor slender rice 1 (SLR1) releases OsNAC120 from inhibition in rice. This release allows OsNAC120 to activate genes involved in GA biosynthesis while simultaneously repressing genes involved in ABA biosynthesis (Xie et al., 2024). As a result, a positive feedback loop for GA accumulation and a negative feedback loop promoting ABA production are established, collectively enhancing growth. Conversely, under drought conditions, increased ABA signaling activates the SnRK2 homolog osmotic stress/ABA-activated protein kinase 9 (OsSAPK9), which phosphorylates OsNAC120 and promotes its degradation. At the same time, drought-induced stabilization of SLR1 further reduces the transcriptional activity of OsNAC120 (Xie et al., 2024). This dual regulation suppresses growth-related genes while activating drought-responsive genes, shifting the balance from growth to stress acclimation. This regulatory mechanism illustrates how plants dynamically modulate hormonal networks to manage the trade-off between survival and growth (Figure 1B).

These discoveries not only enhance our understanding of phytohormone interactions but also provide potential strategies for improving crop performance. Using CRISPR–Cas9 technology to modulate the TSB1 and NAC120 pathways, guided by mechanistic insights from Arabidopsis and rice, could increase stress tolerance while maintaining yield. In addition, leveraging natural genetic variation within these pathways across crop cultivars may facilitate the development of new varieties capable of thriving under challenging environmental conditions, thereby contributing to global food security.

TOR integrates plant growth and stress tolerance

The TOR complex (TORC) is a core regulator of plant growth and development and can be activated by energy and various nutrient signals (Liu and Xiong, 2022). Recent studies have shown that TOR mediates the trade-off between growth and stress responses. Under favorable conditions, inhibition of stress-responsive pathways is crucial for normal growth. For example, TOR kinase phosphorylates the ABA receptor PYL, reducing ABA signaling and facilitating growth recovery after stress subsides (Wang et al., 2018). By contrast, stress- and ABA-activated SnRK2s phosphorylate the regulatory-associated protein of TOR (RAPTOR), a key component of TORC, thereby lowering TOR activity and consequently inhibiting growth (Wang et al., 2018). This conserved phospho-regulatory feedback mechanism allows plants to effectively balance growth and stress responses.

In addition, ABA induces the nuclear-to-cytoplasmic translocation of SnRK1, thereby inhibiting TORC activity and modulating the interaction between SnRK1 and the PP2C–SnRK2 complex (Belda-Palazon et al., 2020, 2022). TOR primarily phosphorylates p70 ribosomal protein S6 kinases (S6Ks) and E2 promoter binding factor (E2F) transcription factors, which are crucial regulators of translation and the cell cycle, respectively (Schepetilnikov et al., 2013; Xiong et al., 2013). Under stress conditions, ABA promotes the phosphorylation of RAPTOR1 by SnRK2s, thereby reducing TOR activity by disrupting the RAPTOR1–TOR interaction (Wang et al., 2018). This reduction in TOR activity decreases the phosphorylation of PYLs, promoting the binding of ABA to PYLs and the activation of SnRK2 (Wang et al., 2018). In the absence of stress, TOR signaling limits ABA and stress responses. Accordingly, inhibition of TOR activity enhances ABA responses, as demonstrated by the raptor1 mutant, which exhibits pronounced ABA hypersensitivity characterized by reduced seed germination and chlorophyll content, together with enhanced induction of ABA-responsive genes (Wang et al., 2018) (Figure 1A). Overall, these findings highlight TOR as a central hub coordinating stress signaling and growth and underscore its reciprocal regulation by SnRK2s during ABA signaling.

SnRK1 proteins are plant orthologs of yeast sucrose non-fermenting 1 (SNF1) and mammalian adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK). They orchestrate extensive metabolic and transcriptional reprogramming to restore homeostasis and enhance survival (Baena-González et al., 2007; Baena-Gonzalez and Sheen, 2008; Nukarinen et al., 2016). In plants, SnRK1s function as primary regulators of cellular energy balance (Xu et al., 2025). Under optimal conditions, SnRK2s interact with PP2Cs and SnRK1s to form a complex that inhibits SnRK1 activity, thereby enabling TOR to promote growth (Belda-Palazon et al., 2020). Conversely, under stress conditions, elevated ABA levels promote ABA binding to PYR/PYL/RCAR receptors and the subsequent inhibition of PP2Cs, thereby promoting dissociation of the SnRK2–PP2C–SnRK1 complex (Belda-Palazon et al., 2020). This activation of SnRK1 suppresses TOR activity, thereby attenuating plant growth and confirming the essential function of SnRKs in mediating the balance between stress responses and growth. Building on these mechanistic insights, future investigations could focus on integrating TOR–SnRK signaling pathways into crop breeding initiatives. Using genetic engineering approaches, crops could be engineered to optimize TOR and SnRK2 expression, thereby enhancing their capacity to balance growth with stress responses. This strategy not only has the potential to increase yield under stress conditions but also establishes a foundation for developing crops capable of thriving in increasingly unpredictable climates.

Nutrient–hormone crosstalk integrates growth and stress signaling

Under abiotic stress, plants activate an ABA-centered program that actively represses growth to enhance survival, even in the absence of an overt energy deficit, underscoring the need to reconcile stress tolerance with growth. Overexpression of ABA-related transcription factors, such as AREB1, AREB2, or ABF3, reduces growth under non-stress conditions but improves survival under drought (Kang et al., 2002; Fujita et al., 2005). Contrary to the assumption that energy deficits are unavoidable under stress, physiological studies have shown that soluble carbohydrate concentrations frequently increase under water scarcity (Hummel et al., 2010; Muller et al., 2011). In addition, in various plant species, growth rates decline more rapidly than photosynthetic rates under stress, although the severity of this decline varies among species (Muller et al., 2011). These observations indicate that stressed plants actively reduce growth (i.e., carbon expenditure) to conserve energy resources. Therefore, a major challenge for plants is to shift from survival-focused strategies to a more integrated approach that harmonizes growth and survival.

Nitrogen (N) and phosphorus (P) are essential nutrients, and deficiencies in either nutrient trigger the biosynthesis of strigolactones (SLs) (Umehara et al., 2010; Yoneyama et al., 2012; Hu et al., 2024). SLs are crucial phytohormones that regulate plant growth and stress responses, particularly under salinity, drought, and temperature extremes (Mostofa et al., 2018; Hu et al., 2024; Qi et al., 2024; Ban et al., 2025; Shi et al., 2025; Sun and Chu, 2025; Zhou et al., 2025). Similar to ABA, SLs can enhance both cold and heat tolerance in tomato (Solanum lycopersicum) (Chi et al., 2021). For instance, GR24, a synthetic SL analog, alleviates salt stress in tomato seedlings by increasing photosynthetic pigment levels and enhancing antioxidant enzyme activities (Liu et al., 2022a). In addition, GR24 improves waterlogging tolerance in grapevine (Vitis vinifera) (Ge et al., 2024). These observations suggest that SLs may help plants cope with abiotic stress. Stimulating SL production under low nitrogen and phosphorus availability could reduce the requirement for these nutrients in drought-prone or saline soils while maintaining adequate SL concentrations to enhance crop resilience to abiotic stress.

NRT1.1B, known primarily as a nitrate transporter and receptor, can also directly sense extracellular ABA (Ma et al., 2025). Upon ABA binding, NRT1.1B interacts with the cytoplasmic repressor protein SPX4, leading to the release of the transcription factor NLP4, which is otherwise sequestered by SPX4. This interaction initiates an ABA-responsive transcriptional program (Ma et al., 2025). In addition, competition between nitrate and ABA for binding to NRT1.1B provides regulatory flexibility, allowing plants to adjust ABA responsiveness in response to fluctuating nutrient conditions and integrate multiple environmental cues (Ma et al., 2025). These findings enhance our understanding of how plants respond to complex environmental stimuli and lay the groundwork for optimizing the balance between growth and stress tolerance in crops (Figure 1C).

Extensive studies have focused on growth regulation and stress responses during acute stress; however, the mechanisms by which plants optimize energy allocation under chronic abiotic stress involve complex trade-offs between growth and stress tolerance (Yang et al., 2014). This complexity is particularly evident under multiple simultaneous stresses. In natural ecosystems, plants often face several stressors simultaneously, resulting in compound stress. Recent multi-omics analyses have shown that molecular responses to combined stresses can be distinct and unpredictable rather than simply additive, as exemplified in tomato (Pardo-Hernández et al., 2025). However, whether ABA–SnRK signaling also plays a central role in responses to combined stresses and what the underlying molecular mechanisms are remain largely unknown, particularly in crops. The precise mechanisms and key regulatory factors that facilitate the transition from a survival-centered state to one that also prioritizes growth during prolonged abiotic stress are also unclear. Investigating these areas is crucial for developing strategies to enhance crop resilience to environmental stressors. Identifying common factors, particularly molecular markers, across different stresses and validating their functions under combined stress, and integrating omics approaches, will provide a deeper understanding of the ABA signaling network and ultimately contribute to the development of stress-tolerant crop varieties. Elucidating the regulatory pathways governing this transition may also reveal novel targets for genetic manipulation.

New insights into SnRK-mediated desensitization of ABA signaling

Plants rapidly accumulate ABA in response to short-term stress, which strongly inhibits growth. However, maintaining elevated ABA levels during prolonged stress is counterproductive. Although plants have developed distinct mechanisms to balance stress responses and growth, continuously adjusting this balance is challenging and requires a constant energy supply. To support basal growth and ensure completion of the reproductive cycle under prolonged stress, desensitization of ABA signaling becomes essential once plants have adapted to stress conditions. A recent study uncovered a molecular mechanism in Arabidopsis thaliana that facilitates acclimation to prolonged ABA exposure (Lu et al., 2024).

During short-term ABA treatment, cytoplasmic SnRK2 proteins translocate to the nucleus, where they phosphorylate downstream transcription factors, thereby activating gene expression and enhancing ABA responses (Soma et al., 2023). In addition, plasma membrane-localized SnRK2.6 interacts with respiratory burst oxidase homologs RBOHD and RBOHF to initiate H₂O₂ signaling (Lu et al., 2024). By contrast, under prolonged ABA treatment, N-glycosylation of SnRK2.2 and SnRK2.3 occurs within the endoplasmic reticulum–Golgi network, promoting their translocation from the nucleus to peroxisomes (Lu et al., 2024). Once in peroxisomes, SnRK2s phosphorylate glucose-6-phosphate/phosphate translocator 1 (GPT1), which plays a pivotal role in regulating reduced nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis at the peroxisomal membrane. This process enhances the oxidative pentose phosphate pathway and reduces oxidative stress caused by H₂O₂ (Lu et al., 2024). Consequently, lower H₂O₂ levels alleviate ABA-induced growth inhibition, thereby improving plant adaptation to adapt to prolonged ABA signaling (Figure 2).

Figure 2.

SnRK2-mediated plant adaptation to prolonged ABA exposure.

Sucrose non-fermenting 1-related kinase 2.6 (SnRK2.6), which is located at the plasma membrane, interacts with respiratory burst oxidase homologs RBOHD and RBOHF to initiate H₂O₂ signaling during normal growth. In response to short-term abscisic acid (ABA) treatment, cytoplasmic SnRK2.2, SnRK2.3, and SnRK2.6 (collectively referred to as SnRK2s) translocate to the nucleus. Once in the nucleus, they phosphorylate downstream transcription factors (TFs), which in turn activate TPST and induce ABA-responsive gene expression (left half of the figure). Under prolonged ABA treatment, SnRK2.2 and SnRK2.3 are translocated from the nucleus to the endoplasmic reticulum (ER), a process mediated by as-yet-unidentified factors (indicated by red arrows). Upon arrival at the ER, these SnRK2s undergo N-glycosylation, facilitating their gradual redistribution to the peroxisomal membrane (right half of the figure). An alternative mechanism may involve an unknown factor that directly facilitates the translocation of newly synthesized SnRK2s to the ER (indicated by red arrows). These processes reduce the nuclear concentration of SnRK2.2 and SnRK2.3, thereby decreasing the transcription of ABA-responsive genes. Within peroxisomes, SnRK2.2 and SnRK2.3 interact with and phosphorylate (P) glucose-6-phosphate/phosphate translocator 1 (GPT1), thereby modulating the availability of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and reducing H₂O₂ levels. Furthermore, in the presence of ABA, ABA-bound PYLs recruit ABI1/2, facilitating the release of SnRK2.6 from ABI1/2. The interaction between HOS15 and SnRK2.6 is also attenuated by ABA, resulting in the stabilization and activation of SnRK2.6. Following activation, SnRK2.6 first undergoes autophosphorylation and then trans-phosphorylates target TFs. Upon removal of ABA, ABI1/2 reassociate with SnRK2.6 and dephosphorylate it, thereby promoting its degradation via HOS15. However, sustained ABA exposure contributes to the destabilization of SnRK2.6 because of ABI1/2 accumulation, thereby triggering desensitization and the restoration of homeostasis. HOS15-mediated degradation of SnRK2.6 enables precise modulation of ABA signaling intensity and facilitates desensitization. In addition, TPST interacts with SnRK2.2, SnRK2.3, and SnRK2.6, leading to their sulfation. Sulfated SnRK2s show markedly reduced stability and are rapidly degraded via the 26S proteasome, thereby attenuating ABA signal transduction and preventing the overactivation of ABA signaling.

S, sulfation; G, glycosylation; P, phosphorylation.

Given the critical role of ABA as a signaling molecule in responses to abiotic stress, it is important to explore whether these desensitization and adaptation mechanisms operate broadly across different ABA-mediated stress responses. Notably, SnRK2s exhibit subcellular redistribution in response to prolonged ABA treatment (Lu et al., 2024). This redistribution not only attenuates ABA signaling but also reflects a transition from transcriptional to metabolic activity during prolonged ABA signaling, contributing to the maintenance of NADPH levels in peroxisomes (Figure 2). This work highlights the dual roles of SnRK2s in ABA responses and their importance in maintaining growth.

The stability of SnRK2.6 plays a crucial role in regulating ABA signal desensitization, a process facilitated by ubiquitination through high expression of osmotically responsive genes 15 (HOS15), a substrate receptor for a CUL4–DDB1-based E3 ubiquitin ligase complex associated with organogenesis, developmental phase transitions, and responses to osmotic and cold stress (Ali et al., 2019). The interaction between HOS15 and SnRK2.6 is stabilized by ABI1/2. Under stress conditions or during ABA treatment, HOS15-induced degradation of SnRK2.6 is inhibited, which enhances plant stress responses (Ali et al., 2019). Conversely, once the ABA signal subsides, the protein phosphatases ABI1/2 promote the rapid degradation of SnRK2.6 through HOS15-mediated pathways (Ali et al., 2019). Notably, even in the presence of ABA, SnRK2.6 levels decrease within hours of signaling initiation, indicating a feedback loop in which SnRK2.6 upregulates ABI1/2, further promoting its own degradation (Ali et al., 2019). These intricate dynamics are essential for understanding ABA-induced stress responses and desensitization. This interplay indicates that SnRK2.6 is regulated through a dynamic feedback network rather than a simple linear pathway. Further studies are warranted to explore the potential of modulating the HOS15–ABI1/2 signaling module to enhance stress tolerance in crops and improve yield stability.

Tyrosine sulfation, catalyzed by tyrosylprotein sulfotransferase (TPST), is a PTM that affects enzymatic activity, protein interactions, and protein stability (Yang et al., 2015; Tanaka et al., 2017; Royek et al., 2022; Zhang et al., 2025a). Mutants lacking TPST exhibit phenotypic traits such as stunted growth, chlorosis, and accelerated senescence in Arabidopsis (Komori et al., 2009; Kaufmann et al., 2021). In addition, TPST is involved in ABA signaling by interacting with SnRK2.2, SnRK2.3, and SnRK2.6 within the Golgi apparatus. This interaction promotes SnRK2 sulfation, leading to increased degradation of these proteins and a subsequent reduction in ABA signaling (Wang et al., 2023). This mechanism represents a novel pathway for ABA desensitization (Figure 2). Moreover, many proteins are regulated through the coordinated action of multiple PTMs, which collectively influence diverse biological processes. This suggests that different types of PTMs may interact with key phytohormone-related proteins, potentially regulating the desensitization of ABA signaling and crop adaptation to prolonged ABA exposure. Such insights are important for advancing agricultural sustainability. Therefore, it is essential to investigate the roles of various PTMs, including methylation, acetylation, ubiquitination, neddylation, and SUMOylation, in responses to prolonged stress and in adaptive mechanisms in crops. Unraveling these complex networks will enhance our understanding of how plants survive and grow under adverse conditions and contribute to crop improvement.

Concluding remarks and perspectives

As climate change imposes increasing environmental pressure, plants must deploy adaptive mechanisms that enhance resilience while maintaining growth and reproductive success. In this context, SnRK2 kinases perform bifunctional roles, coordinating prolonged stress responses while maintaining growth through diverse PTMs (Yang et al., 2019; Lin et al., 2020; Lu et al., 2024). A comprehensive understanding of how ABA regulates plant development and growth is therefore essential for sustainable agriculture. Here, we propose several challenges for future research and potential solutions.

First, CRISPR-mediated locus-specific epigenome editing provides a promising approach for tuning chromatin states without altering coding sequences (Ghoshal et al., 2021; Nakamura et al., 2021; Zhang et al., 2024). For instance, this technique could be used to modify the expression levels of SnRKs or TOR in crops by targeting specific histone modifications, such as H3K4me3 or H3K27me3. In parallel, genome editing could be used to alter key regulatory sites or phosphorylation sites that affect the activity of these kinases. Together, these approaches could regulate the expression or activity of ABA-related kinases, thereby adjusting ABA sensitivity. This strategy has the potential to mitigate growth inhibition while maintaining an optimal level of stress resilience. At the same time, a deeper understanding of crosstalk between ABA and other phytohormones, such as GA, brassinolide (BR), and auxin, could support the development of stress-responsive “growth switches” that minimize yield loss. For instance, stress-inducible promoters that drive the expression of ABA biosynthesis genes could transiently alter the balance between ABA and other phytohormones. This modulation could coordinate phytohormone-mediated stress responses while facilitating rapid post-stress de-repression of growth. Finally, by leveraging natural allelic variation in regulatory regions and using advanced techniques such as multiplex base editing or prime editing, it may be possible to create environmentally stable and finely tuned ABA responses tailored to specific production environments. These strategies could help plants cope with stress while maintaining growth potential, ultimately supporting greater yield stability under fluctuating environmental conditions.

Second, most research has focused on ABA signal activation and acute stress responses, whereas ABA desensitization remains less well understood. To improve crop resilience under prolonged stress, it is crucial to elucidate how SnRK2s mediate ABA desensitization through PTMs beyond the well-characterized mechanisms of N-glycosylation and tyrosine sulfation (Wang et al., 2023; Lu et al., 2024). This phase involves a critical molecular checkpoint at which plants transition from ABA-driven growth repression and rapid stress responses to a desensitized state that balances stress tolerance with ongoing growth. We propose that SnRK2s are key regulators of desensitization under prolonged stress. To test this hypothesis, it will be essential to identify additional regulators of this transition, map the associated signaling and metabolic networks, and track metabolite dynamics throughout the transition. Deciphering this transient checkpoint is crucial for understanding how these components interact during prolonged stress adaptation. Exploring the temporal regulation of this checkpoint may reveal novel targets for crop improvement. Such knowledge will support targeted manipulation of key processes to improve yield stability and adaptation to environmental stress.

Third, a key challenge is to characterize and reengineer ABA flux, transport, and compartmentalization across tissues and organelles, enabling “response zones” (e.g., guard cells and the root endodermis) to mount rapid stress responses while ensuring that “growth zones” (e.g., shoot and root meristems and developing reproductive organs) remain protected from chronic ABA suppression. Translating insights gained from Arabidopsis to agronomically important crops requires the development of spatiotemporal ABA atlases in staple species such as rice, maize, and wheat. This will involve using genetically encoded ABA biosensors in combination with mass spectrometry while integrating single-cell transcriptomics and proteomics to comprehensively map ABA distribution and transporter networks. Once functionally validated orthologs are identified in these crops, their expression levels can be fine-tuned using tissue-specific or inducible and CRISPR-mediated genome-editing techniques to enhance ABA transport and sensitivity within stress-response zones, thereby minimizing ABA-mediated inhibition of growth-promoting regions. The ultimate goal is to engineer stress-tolerant crops that can sustain high yields under adverse environmental conditions.

Funding

This work was supported by the National Natural Science Foundation of China (32470364 and 31872804), the Natural Science Basic Research Program of Shaanxi (2025JC-JCQN-056 and 2024JC-YBMS-151), the Shaanxi Fundamental Science Research Project for Chemistry & Biology (22JHQ054 and 22JHZ007), the Fundamental Research Funds for the Central Universities (D5000230089), the China Postdoctoral Science Foundation (2025M784404), and the Innovation Foundation for Doctoral Dissertations of Northwestern Polytechnical University (ZX2026056).

Acknowledgments

We thank all members of our laboratory for valuable discussions and constructive feedback on this manuscript. The authors declare no competing interests.

Author contributions

W.Z., Y.F., and K.S. wrote the manuscript. K.S. conceived the project. W.Z., Y.F., and K.S. designed and prepared the figures. L-S.P.T., W.L., and K.S. edited the manuscript. All authors contributed to the manuscript and approved the final version.

Published: June 26, 2026