Table 3.

JAKs biological activities

Biological Activity	JAK1	JAK2	JAK3	TYK2
Cytokine Signaling	Involved in signaling pathways activated by various cytokines and growth factors [74, 95, 103, 104] (Mostly type II cytokine receptors (ifnα/β, ifnγ, and IL-10), γc -family cytokines of the c family (IL-2, IL-4, IL-7, IL-9 and IL-15) and gp130-cytokines (IL-6, IL-11, LIF, OSM, CNTF, and CT-1)	Plays a critical role in the signaling of type I cytokines such as EPO, IL-3, GM-CSF; IL-5, TPO, growth hormone, prolactin, G-CSF [119, 121]	Essential for cytokine signaling, particularly the γc-cytokines (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), IL-3, IL-5, and GM-CSF [130, 131]	Associated with various cytokine receptors including IFNAR1, IL-12Rβ1, IL-10R2, IL-23R and gp130 (IL-6, IL-11, and oncostatin M) [143, 144]
Immune response regulation	Regulates immune responses, including activation and differentiation of immune cells	Plays a role in the regulation and modulation of the immune response	Critical for immune response regulation, particularly lymphocyte maturation and function	Involved in the regulation of immune responses, including Th1/Th17 differentiation [143]
			Regulates TLR-mediated inflammatory cytokine production [132]	Is also involved in macrophage differentiation and polarization [149–151]
Antiviral Immune Response	Regulating IFN-γ production, important for the antiviral immune response [103, 108]
Hematopoiesis	Participated in the signaling pathways that regulate hematopoietic cell development, differentiation, and proliferation. Plays a role in the regulation of hematopoietic stem cells [50, 105]	Involved in the signaling pathways that regulate adult hematopoietic stems84	Involved in early lineage decision and differentiation of various cell types in hematopoiesis, including erythrocytes, lymphocytes, and macrophages	Plays a role in myeloid cell differentiation and regulation of hematopoietic stem cells [147, 152]
	It is crucial for the differentiation, development, and function of lymphoid cells [91, 116]		It is crucial for the differentiation, development, and function of lymphoid cells (Obligate partner for Jak1)	Promotes NK cell maturation and enhances their activity [146]
	Participatory in the regulation of myeloid cell development [117, 118]	Plays a role in erythropoiesis, thrombopoiesis, and regulation of myelopoiesis [153]	Play an important role in myeloid cell differentiation [134]
Metabolic action			Contributes to the development of insulin resistance [154]	Associated with impaired glucose tolerance [140]
Other roles	Regulating IFN-γ production, critical role in antitumor immune responses [105, 106]	Essential for erythropoietin (EPO) and thrombopoietin (TPO) receptor signaling [122–124]	Essential for γc-dependent T cells and B cells, and for γc-dependent prevention of c-dependent thymocyte apoptosis (jointly with JAK1) [89]	Involved in NK cell maturation, promotes Th1/Th17 differentiation [143–146]