Table 1 Association of Janus kinases (Jaks), Signal transducers and activators of transcription (Stats), and suppressors of cytokine signaling (SOCSs) with cytokine receptors and phenotype of knockout mice.

Jak1

γ_ccytokines, gp130 cytokines, IL-10, IFN- α , IFN- β , IFN- γ, IL-13

Neurologic defect (?), mice die perinatally

Jak2

Erythropoietin, β_ccytokines, gp130 cytokines, IL-13, IL-12, GH, prolactin, thrombopoietin, IFN- γ

Embryonically lethal, failed to develop red blood cells

Jak3

IL-2, IL-7, IL-15, γ_c cytokines

SCID

Tyk2

gp130 cytokines, IL-13, IL-12, IFN-α, IFN-β, IL-10

Not yet reported

Stat1

IFN- α , IFN- β , IFN- γ , IL-2, IL-6, IL-10

Susceptibility to viral and some bacterial infections

Defective signaling in response to IFNs

Impaired tumor rejection

Stat2

IFN-α, IFN-β

Defective signaling in response to IFNs*

Stat3

LIF, IL-10, IL-6, other gp130 cytokines, γ_c cytokines, GH

Embryonically lethal

Targeted disruption in macrophages and neutrophils showed defective

IL-6 and IL-10 signaling

Chronic enterocolitis

Conditional knockouts showed suppressed epithelial apoptosis and

delayed mammary gland involution

Stat4

IL-12

Defective Th1 development

Stat5a

Prolactin, other γ_c cytokines, otherβ_c cytokines, GH, thrombopoietin

Defective lobuloalveolar development in breast

Stat5b

GH, other γ_c cytokines,β_c cytokines, prolactin, thrombopoietin

Required for sexual dimorphism

Stat5a/b

GH, IL-2, erythropoietin

Infertile, smaller body size

Impaired cell-cycle progression of peripheral T cells

Fetal anemia (?)

Stat6

IL-4, IL-13

Defective Th2 development

Stat4/6

No Th2 cells in vitro

SOCS-1

IFN- γ, IL-6, GH, thrombopoietin, OSM, LIF

Perinatal lethality, hyper-responsiveness to IFN-γ

SOCS-3

Erythropoietin, GH, IL-2, leptin, CNTF, IL-11, IL-10

Embryonic lethality, ? due to erythrocytosis