Janus kinase-signal transducer and activator

Matsuda T, Ferreri K, Todorov I, Kuroda Y, Smith CV, Kandeel F, Mullen Y. 2005. Silymarin protects pancreatic -cells against cytokine-mediated toxicity Implication of c-Jun NH2-terminal kinase and Janus kinase/signal transducer and activator of... 

Carvalho CR, Carvalheira JB, Lima MH, et al. Novel signal transduction pathways for luteinizing hormone and interaction with insulin activation of Janus kinase/ signal transducer and activator of transcription and phosphoinositol 3 kinase/Akt pathways. Endocrinology 2003 144 638-647. 

Janus kinase - signal transducer and activator of transcription... 

The Janus Family Tyrosine Kinases-Signal Transducers and Activators of Transcription Signaling Pathway... 

Leptin signalling is via monomeric receptors in the brain. A short-form of the leptin receptor (Lep-R) is required to transport the hormone across the blood-brain barrier and a long-form Lep-R is located in the hypothalamus. The long-form is functionally linked with a particular type of receptor-associated tyrosine kinase called Janus kinase (JAK, see Section 4.7) whose function is to phosphorylate a STAT (signal transducer and activator of transcription) protein a similar mechanism to that often associated with signalling by inflammatory cytokines. 

A variation on the basic theme of receptor Tyr kinases is seen in receptors that have no intrinsic protein kinase activity but, when occupied by their ligand, bind a soluble Tyr kinase. One example is the system that regulates the formation of erythrocytes in mammals. The cytokine (developmental signal) for this system is erythropoietin (EPO), a 165 amino acid protein produced in the kidneys. When EPO binds to its plasma membrane receptor (Fig. 12-9), the receptor dimerizes and can now bind the soluble protein kinase JAK (Janus kinase). This binding activates JAK, which phosphory-lates several Tyr residues in the cytoplasmic domain of the EPO receptor. A family of transcription factors, collectively called STATs (signal transducers and activators of transcription), are also targets of the JAK kinase activity. An SH2 domain in STATS binds (P)-Tyr residues in the EPO receptor, positioning it for this phosphorylation by JAK. When STATS is phosphorylated in re-... 

The leptin signal is transduced by a mechanism also used by receptors for interferon and growth factors, the JAIC-STAT system (Fig. 23-34 see Fig. 12-9). The leptin receptor, which has a single transmembrane segment, dimerizes when leptin binds to the extracellular domain of two monomers. Both monomers are phos-phorylated on a Tyr residue of the intracellular domain by a Janus kinase (JAK). The -Tyr residues become docking sites for three proteins that are signal transducers and activators of transcription (STATs 3, 5, and 6, sometimes called fat-STATS). The docked STATs are then phosphorylated on Tyr residues by the... 

Fig. 6.5 Activation of the Jak/STAT pathway by angiotensin II. Binding of angiotensin II to the ATi receptor stimulates, via a G protein, the phosphorylation of janus family kinases (JAK). Jak2 participates in the phosphorylation and activation of signal transducers and activators of transcription (STAT) family members, which translocate to the nucleus and upregulate growth-linked genes.

Incorporation of cytokine in a naive Th lymphocyte receptor activates the route of Janus kinases (JAK1, JAK2, JAK3), transmission proteins for intracellular signals, and activating transcriptions—Signal Transducer and Activator Transcription (STAT)—consequently phosphorylation of receptor tyrosine results. 

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway play a critical role in the signalling of a wide array of cytokines and growth factors, leading to various cellular functions, including proliferation, growth, haematopoiesis and immune response. 

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