M A R C B L

D. Cytokine Receptors

Cytokine receptors are associated at the intracellular domain of the receptor with soluble cytoplasmic tyrosine kinases called JAKs [116]. Upon binding a ligand, a cytokine receptor will dimerize and result in the activation of receptor-associated JAK1 and JAK2 by transphosphorylation (Fig. 20). The activated JAKs phosphorylate tyrosine in the endodomains of the receptor distal to the JAK binding domain. These receptor phosphotyrosines and the 4-5 carboxy proximal amino acids constitute the SH2 binding/recognition domain for SH2 domains of STATs. Appropriate STATs are recruited to the phosohorylated receptor forming a complex with receptor. At the receptor, JAKs phosphorylate STATs on a conserved tyrosine. Activated (phosphorylated) STATs are released from the receptor and dimerize through the interaction of the SH2 domain of one STAT with

Figure 20 Schematic illustration of cytokine signal-transduction pathways. Upon ligand binding, the cytokine receptor dimerizes and activates Jak kinases associated with the receptor, which phosphorylated tyrosine residues of the receptor. STAT proteins are recruited to the receptor and bind through SH2 domain where they are phosphorylated on tyrosine by JAKs. Activated STATs are released and dimerize by interacting with SH2 one with the PY of the other and vice versa. The STAT dimer translocated into the nucleus where it binds to the enhancer and activates transcription.

Figure 20 Schematic illustration of cytokine signal-transduction pathways. Upon ligand binding, the cytokine receptor dimerizes and activates Jak kinases associated with the receptor, which phosphorylated tyrosine residues of the receptor. STAT proteins are recruited to the receptor and bind through SH2 domain where they are phosphorylated on tyrosine by JAKs. Activated STATs are released and dimerize by interacting with SH2 one with the PY of the other and vice versa. The STAT dimer translocated into the nucleus where it binds to the enhancer and activates transcription.

Was this article helpful?

0 0

Post a comment