. 2021 Aug 20;12:734917. doi: 10.3389/fphar.2021.734917

TABLE 2.

Identified protein kinases in ANG II signaling in cardiovascular system.

S. No.	Kinase	Associated physiology	References
Ser/Thr kinase
1.	ERK	Stimulate NADPH oxidase and ROS generation causing hypertrophy, hyperplasia, and migration of VSMCs	Moraes et al. (2017)
			Chen et al. (2020)
			Ge et al. (2021)
2.	JNK	Cardiac hypertrophy	Xu et al. (2021)
3.	P38	Cardiac hypertrophy	Xu et al. (2021)
4.	MAPK	Cardiac hypertrophy, hyperplasia and migration of VSMCs	Chen et al. (2020)
5.	GRK	Regulate function of GPCR	Rukavina Mikusic et al. (2020)
			Murga et al. (2019)
			Brinks and Eckhart (2010)
6.	ROCK	Fibrosis and involved in TGF-β1-induced atrial remodeling.	Brinks and Eckhart (2010)
6.	ROCK	Fibrosis and involved in TGF-β1-induced atrial remodeling.	Bai et al. (2021); Liu et al. (2016)
7.	PAK1	Attenuation of cardiac fibrosis and hypertrophy	Zhou et al. (2021)
8.	Raf	Phosphorylates and activates the MAPK kinase, MEK-1, which, in turn, phosphorylates and activates MAPK.	Ge et al. (2021)
9.	MLCK	Regulating cardiac muscle contraction and hypertrophy	Wang et al. (2017)
10.	CaMKII	Regulates Erk1/2 and Akt-dependent signaling in VSMC	Li et al. (2010)
11.	IKK	Triggers myofibroblast survival	Xu et al. (2021)
11.	IKK	Triggers myofibroblast survival	Cao et al. (2021)
12.	PI3K	Stimulate NADPH oxidase and ROS generation causing hypertrophy, hyperplasia and migration of VSMCs	Zhong et al. (2021)
			Cheng et al. (2021)
			Gao et al. (2021)
13.	P70S6K	Stimulate NADPH oxidase and ROS generation causing hypertrophy, hyperplasia and migration of VSMCs	Gao et al. (2021)
14.	Akt	Stimulate NADPH oxidase and ROS generation causing hypertrophy, hyperplasia and migration of VSMCs	Gao et al. (2021)
14.	Akt		Kim et al. (2012)
15.	mTOR	Cell proliferation, motility and protein synthesis	Kim et al. (2012)
16.	PERK	Inhibition of protein synthesis	Fang et al. (2020)
16.	PERK	Inhibition of protein synthesis	Lins et al. (2021)
17	AMPK	Preventive in AAA, endothelial dysfunction	Chen et al. (2020)
18.	ALK1/2/4	Central regulation of hypertension, cardiac fibrosis, cardiac hypertrophy	González-Núñez et al. (2015)
19.	MNK	Attenuation of cardiac fibrosis and hypertrophy	Kasuya et al. (2021)
19.	MNK	Attenuation of cardiac fibrosis and hypertrophy	Yuan et al. (2016)
20.	WNK	Hypertension and vascular contraction	Simoes et al. (2020)
			Shao et al. (2021)
			Brown et al. (2021)
21.	SPAK	Hypertension and vascular contraction	Shao et al. (2021)
21.	SPAK	Hypertension and vascular contraction	Brown et al. (2021)
22.	MKK4	Atrial fibrosis via kinase activation	Fang et al. (2020)
22.	MKK4	Atrial fibrosis via kinase activation	Li et al. (2017)
23.	TRPM7	Implicated in cardiac fibrosis	Zhong et al. (2018)
24.	DAPK	Vascular constriction via kinase activation	Usui et al. (2012)
25.	SGK1	Cardiac remodelling	Ock et al. (2021)
26.	PKD1	Cardiac hypertrophy and fibrosis	Weber et al. (2004); An et al. (2020)
27.	PKC	Stimulate NADPH oxidase and ROS generation causing hypertrophy, hyperplasia and migration of VSMCs	Wang J. et al. (2020)
28.	PKA	Cardiac hypertrophy	Wang J. et al. (2020)
28.	PKA	Cardiac hypertrophy	Dai et al. (2019)
Tyrosine kinase
1.	Axl	Inhibitor of innate immunity	Berk and Corson, (1997)
1.	Axl	Inhibitor of innate immunity	Batchu et al. (2016)
2.	Src	Hypertension and hypertrophy	Callera et al. (2016)
			Luo et al. (2020)
			Touyz et al. (2002)
			Berk and Corson, (1997)
3.	BMX	Cardiac hypertrophy via endothelial activation	Holopainen et al. (2015)
3.	BMX	Cardiac hypertrophy via endothelial activation	Mitchell-Jordan et al. (2008)
4.	sFLT-1	Anti-angiogenic	Berk and Corson, (1997)
5.	FAK	Enhance protein synthesis	Berk and Corson, (1997)
6.	PYK2	Allows growth-promoting signal by Ang II in VSMC	Gao J. et al. (2020)
6.	PYK2	Allows growth-promoting signal by Ang II in VSMC	Jain et al. (2021)
7.	JAK	Mediates Ang II triggered gene transcription	Han et al. (2018)
8.	EGF	Cell hypertrophy and remodeling	Vukelic and Griendling, (2014)
8.	EGF	Cell hypertrophy and remodeling	Peng et al. (2016)
9.	PDGF	Cardiac remodeling	Weber et al. (2004)
9.	PDGF	Cardiac remodeling	Touyz et al. (2002)
10.	IGF	Cardiac remodeling and hypertension	Ock et al. (2021)
11.	FGF-2	Cardiac hypertrophy	Li et al. (2019)
11.	FGF-2	Cardiac hypertrophy	Liu et al. (2020)

Akt, Protein kinase B; ALK, activin receptor-like kinase; AMPK, AMP-activated protein kinase; BCR, breakpoint cluster region protein; CaMKII, calmodulin-dependent protein kinase II; DAPK, death-associated protein kinase; EGF, Epidermal growth factor; EKR, extracellular-signal-regulated kinase; FAK, Focal adhesion kinase; FGF-2, Fibroblast growth factor; GRK, G protein-coupled receptor kinase; IGF, Insulin like growth factor 1; IKK, IκB kinase, JAK, Janus kinase; JNK, c-Jun N-terminal kinase; MAPK, Mitogen activated protein kinase; MKK4, mitogen-activated protein kinase kinase 4; MLCK, Myosin light chain kinase; MNK1, mitogen-activated protein kinase-interacting kinase 1; mTOR, Mammalian target of rapamycin; P70S6K, Ribosomal protein S6 kinase beta-1 PAK1, p21-activated kinase 1; PDGF, Platelet derived growth factor; PERK, protein kinase R-like ER kinase; PI3K, Phosphatidylinositol 3-kinase; PK, Protein kinase; PKD1, protein kinase D1; ROCK, Rho-associated protein kinases; Raf, Rapidly accelerated fibrosarcoma; Sflt-1, Soluble fms-like tyrosine kinase-1; SGK1, serum-glucocorticoid regulated kinase 1; SPAK, STE20/SPS1-related proline/alanine-rich kxinase; TRPM7, transient receptor potential 7; WNK, with no lysine kinase.