Phosphorylation initiated dimerization

Fig. 44.16. C54okine signaling through the JAK/STAT pathway. 1. Cytokine binding to receptors initiates dimerization and activation of the JAK kinase, which phosphorylates the receptor on tyrosine residues. 2. STAT proteins bind to the activated receptors and are themselves phosphorylated. 3. Phosphorylated STAT proteins dimerize, travel to the nucleus, and initiate gene transcription. 4. One of the proteins whose s5mthesis is stimulated by STATs is SOCS (suppressor of cytokine signaling), which inhibits further activation of STAT proteins (circle 5) by a variety of mechanisms.

Fig. 1.56. Control of eIF-2 by phosphorylation. Phosphorylated eIF-2 GDP binds strongly to eIF-2B without nucleotide exchange occurring. Initiation of protein biosynthesis is not possible in this case.In reticulocytes, eIF-2 is subject to phosphorylation by the heme-regulated eIF-2-kinase (HRI). The activity of the dimeric HRI is regulated via the heme concentration. Another protein kinase that can phosphorylate and regulate eIF-2 is the RNA-dependent eIF2a-kinase (PKR). The latter is induced by interferons and activated by double stranded RNA.

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