Back to Pathways

Interactive Pathways & Processes

Show Categories

Jak/STAT Signaling Pathway

Click on one of the cytokine subfamilies or receptor type to see the specific Jak and STAT molecules activated by members of the family.

Get Print Copy

IFN-alpha/beta

IFN-alpha/
beta R

Tyk2

Jak1
Jak2

STAT1
STAT2
STAT3
STAT4
STAT5
STAT6

STAT
Dimer

IRF9

STAT Dimer

IRF9

IFN-gamma

IFN-
gamma R

Jak1
Jak2
Tyk2

STAT1
STAT2
STAT3
STAT5
STAT6

STAT
Dimer

STAT Dimer

EGF

EGF R/
ErbB1

Src

Jak1
Jak2

STAT1
STAT3
STAT5

STAT
Dimer

STAT Dimer

Erythropoietin

Erythropoietin R

Jak2
Jak3

STAT1
STAT3
STAT5

STAT
Dimer

STAT Dimer

IL-6

IL-6 R

Jak1
Jak2
Tyk2

STAT1
STAT3

STAT
Dimer

STAT Dimer

IL-2

IL-2 R

Jak1
Jak2
Jak3

STAT1
STAT3
STAT4
STAT5
STAT6

STAT
Dimer

STAT Dimer

IL-3

IL-3 R

Src

Jak1
Jak2
Tyk2

STAT3

STAT1
STAT3
STAT5
STAT6

STAT
Dimer

STAT Dimer

IL-10

IL-10 R

Jak1
Jak2
Tyk2

STAT1
STAT3
STAT5

STAT
Dimer

STAT Dimer

IL-12

IL-12 R

Jak2
Tyk2

STAT1
STAT3
STAT4
STAT5
STAT6

STAT
Dimer

STAT Dimer

Angiotensin II

AGTR-1

G Protein

PLC-beta

PIP₂

IP₃

DAG

Ca²⁺

PKC
delta

PYK2

Jak2

SHP-2

Jak1
Jak2
Tyk2

STAT1
STAT2
STAT3
STAT5
STAT6

STAT
Dimer

STAT Dimer

CXCL12/
SDF-1
alpha

CXCR4

Jak1
Jak2
Jak3
Tyk2

STAT1
STAT2
STAT3
STAT4
STAT5

STAT
Dimer

STAT Dimer

ISRE

Anti-viral

GAS

Type I-II Interferons
Ligand	Receptor Complex	Activated Jak	Activated STAT
IFN-alpha	IFN-alpha-beta R1 +	Jak1	STAT1
	IFN-alpha-beta R2	Jak2	STAT2
		Tyk2	STAT3
			STAT4
			STAT5
			STAT6
IFN-beta	IFN-alpha-beta R1 +	Jak1	STAT1
	IFN-alpha-beta R2	Jak2	STAT2
		Tyk2	STAT3
			STAT4
			STAT5
			STAT6
IFN-gamma	IFN-gamma R1-CD119 +	Jak1	STAT1
	IFN-gamma R2	Jak2	STAT2
		Tyk2	STAT3
			STAT5
			STAT6

Cell Migration

Receptor Tyrosine Kinases
Ligand	Receptor Complex	Activated Jak	Activated STAT
Angiopoietin-2	Tie-2		STAT3
			STAT5
BDNF	TrkB	Jak2	STAT1
			STAT3
EGF	EGF R/ErbB1	Jak1	STAT1
		Jak2	STAT3
			STAT5
EGF	ErbB2/Her2	Jak2	STAT1
			STAT3
			STAT5
EGF	ErbB4/Her4	Jak2	STAT1
			STAT5
Ephrin-A	EphA4	Jak2	STAT1
			STAT3
FGF	FGF R1	Jak1	STAT1
	FGF R2	Jak2	STAT3
	FGF R3	Jak3	STAT5
	FGF R4	Tyk2
Gas6	Mer		STAT3
			STAT5
			STAT6
HGF	HGF R/c-MET	Jak1	STAT1
		Jak2	STAT3
			STAT5
IGF-I	IGF-I R	Jak1	STAT3
		Jak2	STAT5
M-CSF	M-CSF R	Jak1	STAT1
		Tyk2	STAT3
			STAT5
PBEF/Visfatin	Insulin R/CD220	Jak2	STAT3
PDGF	PDGF R alpha	Jak1	STAT1
	PDGF R beta	Jak2	STAT3
		Tyk2	STAT5
			STAT6
SCF/c-kit Ligand	SCF R/c-kit	Jak2	STAT1
			STAT3
			STAT5
VEGF	VEGF R1/Flt-1	Jak2	STAT1
	VEGF R2/KDR/Flk-1	Tyk2	STAT3
	VEGF R3/Flt-4		STAT5
			STAT6

Hematopoietic Cell
Differentiation and Proliferation

Homodimeric Hormone Receptors
Ligand	Receptor Complex	Activated Jak	Activated STAT
Erythropoietin	Erythropoietin R	Jak2	STAT1
		Jak3	STAT3
			STAT5
Growth Hormone	Growth Hormone R	Jak1	STAT1
		Jak2	STAT3
			STAT5
Prolactin	Prolactin R	Jak1	STAT1
		Jak2	STAT3
			STAT5
Thrombopoietin/Tpo	Thrombopoietin R/Tpo R	Jak2	STAT1
		Tyk2	STAT3
			STAT5

Immune Cell Differentiation
Inflammation

Il-6 Family
Ligand	Receptor Complex	Activated Jak	Activated STAT
Cardiotrophin-1/	CT-1 R alpha +	Jak1	STAT1
CT-1	LIF R alpha +	Jak2	STAT3
	gp130	Tyk2	STAT5
CLF/CLC	CNTF R alpha +	Jak1	STAT1
	LIF R alpha +	Jak2	STAT3
	gp130	Tyk2
CNTF	CNTF R alpha +	Jak1	STAT1
	LIF R alpha +	Jak2	STAT3
	gp130	Tyk2
G-CSF*	G-CSF R/	Jak1	STAT1
	CD114	Jak2	STAT3
		Tyk2	STAT5
IL-6	IL-6 R alpha +	Jak1	STAT1
	gp130	Jak2	STAT3
		Tyk2
IL-11	IL-11 R alpha +	Jak1	STAT1
	gp130	Jak2	STAT3
		Tyk2
IL-31	IL-31 RA +	Jak1	STAT1
	OSM R beta	Jak2	STAT3
			STAT5
Leptin/OB*	Leptin R	Jak1	STAT1
		Jak2	STAT3
			STAT5
			STAT6
LIF	LIF R alpha +	Jak1	STAT1
	gp130	Jak2	STAT3
		Tyk2	STAT5
Oncostastin M/	OSM R beta +	Jak1	STAT1
OSM	gp130	Jak2	STAT3
	LIF R alpha +	Tyk2	STAT5
	gp130		STAT6
*G-CSF and Leptin/OB are often associated with the IL-6 family of cytokines because the G-CSF and Leptin receptors are structurally similar to gp130.

Immune Cell Development
Proliferation and Differentiation

Common gamma Chain Receptor Family
Ligand	Receptor Complex	Activated Jak	Activated STAT
IL-2	CD25/IL-2 R alpha +	Jak1	STAT1
	IL-2 R beta +	Jak2	STAT3
	Common gamma Chain/IL-2 R gamma	Jak3	STAT4
			STAT5
			STAT6
IL-4	IL-4 R alpha +	Jak1	STAT1
	Common gamma Chain/IL-2 R gamma	Jak2	STAT3
	IL-4 R alpha +	Jak3	STAT4
	IL-13 R alpha 1	Tyk2	STAT5
			STAT6
IL-7	IL-7 R alpha/CD127 +	Jak1	STAT1
	Common gamma Chain/IL-2 R gamma	Jak3	STAT2
			STAT3
			STAT5
			STAT6
IL-9	IL-9 R +	Jak1	STAT1
	Common gamma Chain/IL-2 R gamma	Jak3	STAT3
		Tyk2	STAT5
IL-13**	IL-13 R alpha 1 +	Jak1	STAT1
	IL-4 R alpha	Jak2	STAT3
		Jak3	STAT5
		Tyk2	STAT6
IL-15	IL-15 R alpha +	Jak1	STAT1
	IL-2 R beta +	Jak2	STAT2
	Common gamma Chain/IL-2 R gamma	Jak3	STAT3
		Tyk2	STAT4
			STAT5
			STAT6
IL-21	IL-21 R +	Jak1	STAT1
	Common gamma Chain/IL-2 R gamma	Jak3	STAT3
			STAT4
			STAT5
TSLP***	IL-17 R alpha/CD127 +	Jak1	STAT1
	TSLP R	Jak2	STAT3
			STAT5
IL-13 is often associated with the Common gamma Chain receptor family because it binds to the same receptor complex and possesses similar biologic properties as IL-4. *TSLP is considered to be a IL-7-related cytokine as it shares several functions and a receptor subunit with IL-7.

Hematopoietic Cell
Growth and Survival

Common beta Chain Receptor Family
Ligand	Receptor Complex	Activated Jak	Activated STAT
GM-CSF	GM-CSF R alpha +	Jak1	STAT1
	Common beta Chain	Jak2	STAT3
			STAT5
			STAT6
IL-3	IL-3 R alpha/CD123 +	Jak1	STAT1
	Common beta Chain	Jak2	STAT3
		Tyk2	STAT5
			STAT6
IL-5	IL-5 R alpha/CD125 +	Jak1	STAT3
	Common beta Chain	Jak2	STAT5

Regulation of Inflammation
T-Cell Dependent Immunity

IL-12 Family
Ligand	Receptor Complex	Activated Jak	Activated STAT
IL-12	IL-12 R beta 1 +	Jak2	STAT1
	IL-12 R beta 2	Tyk2	STAT3
			STAT4
			STAT5
			STAT6
IL-23	IL-12 R beta 1 +	Jak2	STAT1
	IL-23 R	Tyk2	STAT3
			STAT4
			STAT5
IL-27	IL-27 R alpha/WSX-1/ TCCR +	Jak1	STAT1
	gp130	Jak2	STAT2
		Tyk2	STAT3
			STAT4
			STAT5
			STAT6
IL-35	IL-12 R beta 2 +		STAT1
	gp130		STAT4

Immune Responses
Anti-viral
Anti-inflammation

IL-10 Family
Ligand	Receptor Complex	Activated Jak	Activated STAT
IL-10	IL-10 R alpha +	Jak1	STAT1
	IL-10 R beta	Jak2	STAT3
		Tyk2	STAT5
IL-19	IL-20 R alpha +	Jak1	STAT3
	IL-20 R beta	Jak2
IL-20	IL-20 R alpha +	Jak2	STAT3
	IL-20 R beta		STAT5
	IL-22 R alpha 1 +
	IL-20 R beta
IL-22	IL-22 R alpha 1 +	Jak1	STAT1
	IL-10 R beta	Tyk2	STAT3
			STAT5
IL-24	IL-20 R alpha +	Jak1	STAT1
	IL-20 R beta	Jak1	STAT1
	IL-22 R alpha 1 +	Jak1	STAT1
	IL-20 R beta		STAT3
IL-26/AK155	IL-20 R alpha +		STAT1
	IL-10 R beta		STAT3
IL-28A/IFN-	IL-10 R beta +	Jak2	STAT1
lambda 2	IL-28 R alpha/IFN-lambda R1		STAT2
			STAT3
IL-28B/IFN-	IL-10 R beta +		STAT1
lambda 3	IL-28 R alpha/IFN-lambda R1		STAT2
IL-29/IFN-	IL-10 R beta +	Jak1	STAT1
lambda 1	IL-28 R alpha/IFN-lambda R1	Tyk2	STAT2
			STAT3
			STAT4
			STAT5

Vascular Remodeling

Cell Migration

G Protein-Coupled Receptors
Ligand	Receptor Complex	Activated Jak	Activated STAT
Angiotensin II	AGTR-1	Jak1	STAT1
		Jak2	STAT2
		Tyk2	STAT3
			STAT5
			STAT6
Bradykinin	Bradykinin RB2/	Jak2	STAT3
	BDKRB2	Tyk2
Catecholamines	alpha-1A Adrenergic R/	Jak2	STAT1
	ADRA1A	Tyk2	STAT3
	alpha-1B Adrenergic R/
	ADRA1B
	alpha-1D Adrenergic R/
	ADRA1D
CCL2/JE/MCP-1	CCR2	Jak2	STAT1
			STAT3
			STAT5
CCL15/MIP-1 delta	CCR1	Jak1	STAT1
			STAT3
Coagulation Factor II/	PAR1	Jak1	STAT1
Thrombin	PAR3	Jak2	STAT3
	PAR4	Tyk2	STAT5
CXCL12/SDF-1	CXCR4	Jak1	STAT1
		Jak2	STAT2
		Jak3	STAT3
		Tyk2	STAT4
			STAT5
Platelet-activating	PAFR	Jak2	STAT1
Factor (PAF)		Tyk2	STAT2
			STAT3
			STAT5
RANTES/CCL5	CCR5	Jak1	STAT1
		Jak2	STAT3
		Jak3	STAT5
Serotonin (5-HT)	5-HT2A	Jak1	STAT1
		Jak2	STAT3

Overview of Jak/STAT Signaling Pathway

The Jak/STAT pathway is a putative intracellular signaling pathway that mediates the effects of a large number of cytokines and growth factors. These compounds generally bind to receptors that lack intrinsic kinase activity and thus utilize intracellular enzymes to initiate downstream signaling. This signaling pathway is relatively straightforward as it includes only two main components: Janus Kinases (Jaks) and Signal Transducers and Activators of Transcription (STATs). Jak proteins are non-receptor tyrosine kinases that are constitutively associated with the cytoplasmic domain of receptors. The Jak family includes Jak1, Jak2, Jak3, and Tyk2 (Tyrosine Kinase 2). STAT proteins are latent transcription factors that reside in the cytoplasm until activated via phosphorylation, at which time they translocate to the nucleus. Seven STAT family members have thus far been identified: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6.

The Jak/STAT pathway is activated following binding of a cytokine or growth factor to its respective receptor. Receptor engagement by a ligand initiates oligomerization of the receptor chains allowing the associated Jak proteins to activate each other by reciprocal tyrosine phosphorylation. The activated Jaks subsequently phosphorylate specific tyrosine residues in the intracellular domains of the receptor. These phosphorylated residues serve as docking sites for the Src homology 2 (SH2)-domain of STAT proteins. Once bound to the receptor, STAT proteins are phosphorylated by Jaks or other kinases, such as Src. Phosphorylated STATs dissociate from the receptor, dimerize, and then translocate to the nucleus where they complex with other nuclear proteins and bind to specific sequences to regulate the expression of target genes.

To date, over 50 cytokines and growth factors have been shown to utilize the four Jak proteins and seven STAT molecules to regulate cell growth, survival differentiation, motility, and immune responses. Activators of the Jak/STAT signaling pathway include type I/II Interferons, the IL-6, IL-10, IL-12, Common gamma Chain, and Common beta Chain families of cytokines, and numerous growth factors that signal through homodimeric hormone receptors, receptor tyrosine kinases, and G protein-coupled receptors. These receptors activate the same general Jak/STAT pathway, though several notable differences occur. STAT1 and STAT2 activated by type I Interferons associate with Interferon Regulatory Factor 9 (IRF9), also called ISGF3-gamma, to form an Interferon-Stimulated Gene Factor-3 (ISGF3) complex. This complex translocates to the nucleus and binds to the interferon-sensitive response element (ISRE). Additionally, Angiotensin II activates the Jak/STAT pathway by two mechanisms. It stimulates the association of Jak proteins, followed by their subsequent phosphorylation, to the Angiotensin II Receptor, Type 1 (AGTR-1) via the tyrosine phosphatase SHP-2. Angiotensin II also stimulates Jak phosphorylation by Proline-rich Tyrosine Kinase 2 (PYK2) via the PLC-IP3-Ca²⁺- and PLC-DAG-PKC-delta-mediated pathways.

This interactive pathway illustrates a comprehensive list of all Jak and STAT proteins reported to be activated by the different receptor families. It is generally accepted that receptors preferably signal through specific Jak and STAT proteins. However, several factors, such as expression profiles of Jak and STAT proteins, the presence of regulatory molecules, and crosstalk from other signaling pathways, can influence which Jak and STAT proteins are activated by a receptor. To view the references for this information, please visit our Jak/STAT reference table.

To learn more, please visit our Jak/STAT Signaling Research Area.

Get Print Copy of this Pathway

First Name *

Last Name *

Email Address *

Institution *

Job Title

Department

Address 1 *

Address 2

City *

State

Postal Code *

Country

Pathway

May we contact you?

By checking this box, I agree to receive relevant marketing communications regarding products, industry news, literature, and events from Bio-Techne and its brands: R&D Systems, Novus Biologicals, Tocris Bioscience, ProteinSimple and Advanced Cell Diagnostics. I understand that I can change my preferences at any time. I further understand that any data provided to Bio-Techne and its brands will be stored, used, and deleted consistent with Bio-Techne’s Privacy Notice.

Leave this field blank