Signaling by the cytokine receptor superfamily: JAKs and STATs

Thrombopoietin, c‐Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists‐induced aggregation in platelets in vitro

“…3Aa and 3Ba). As it is generally accepted that tyrosine phosphorylation of JAKs is associated with the activation of kinase activity [13,23], TPO treatment increased in vitro kinase activity of Tyk2 and JAK2 in parallel with tyrosine phosphorylation of these kinases (data not shown).…”

“…The cytokine receptor superfamily, which lacks a tyrosine kinase domain, couples ligand binding with the induction of protein-tyrosine phosphorylation that is essential for cytokine signaling [11]. The Janus tyrosine kinase (JAK) family, JAK1, JAK2, JAK3, and Tyk2, and the STAT (for signal transducers and activators of transcription) family are activated through phosphorylation on tyrosine in response to cytokines and growth factors [12,13]. JAKs and STATs provide novel common pathways shared by the receptors for various cytokines or growth factors.…”

Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis

“…All these three signal transduction cascades have been shown to be involved in antiapoptotic effects of Epo on erythroblasts. 14,15 Akt, a serine/threonine protein kinase, was identified as a downstream component in survival signaling through PI3-K. 23 Western blot analysis of retinal lysates of Epo-treated rats revealed a significant upregulation of p-Akt when compared to vehicle-treated controls (Figure 3a). The expression of the unphosphorylated, inactive Akt protein was the same in all samples analyzed.…”

“…14 Several intracellular signal transduction cascades are involved in the antiapoptotic effects of Epo on erythroblasts including Ras-mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3-K), and the Bcl-2 family. 14,15 It is becoming increasingly clear that Epo has additional neuroprotective effects in different in vivo models of brain injury, [16][17][18][19] modulating the same signal transduction cascades that we identified to be involved in RGC death in our MOG-EAE model, the Bcl-2 family and the PI3-K/Akt pathway. 10 Furthermore, Epo has been demonstrated to delay the onset and to reduce the severity of clinical symptoms in an EAE model induced by myelin basic protein (MBP).…”

Pharmaceutical intervention in the JAK/STAT signaling pathway

“…The STAT dimer binds to speci®c DNA response elements within various promoters and activates transcription of downstream genes, leading to an altered cell phenotype. Ihle et al, 1994). Asthma GM-CSF STAT5 JAK2 Myeloid reconstitution IL-6 STAT1, STAT3 JAK1, JAK2, Tyk2 Inflamm., osteoporosis IL-11 STAT3 JAK1, JAK2, Tyk2 Platelet production LIF STAT3 JAK1, JAK2, Tyk2 OSM STAT1, STAT3 JAK1, JAK2, Tyk2 CNTF STAT3 JAK1, JAK2, Tyk2 CNS CT-1 STAT3 JAK1, JAK2, Tyk2 Cardiovascular Leptin STAT3, -1, -5 JAK2 Obesity IL-12 STAT4, STAT3 Tyk2, JAK2 Immune regulation G-CSF STAT3, STAT5 JAK1, JAK2 Myeloid reconstituion Epo STAT5 JAK2 Anemia Tpo STAT5 JAK2 Platelet production Prolactin STAT5 JAK2 GH STAT5, -3, -1 JAK2 GH insufficiency, aging CSF-1/M-CSF STAT1, STAT3 ?…”