Aa

Plasma membrane

Receptor

Activated receptor

A signaling pathway for tyrosine ki-nase receptors. Binding of agonist to the tyrosine kinase receptor (TK) causes dimerization, activation of the intrinsic tyrosine kinase activity, and phosphorylation of the receptor sub-units. The phosphotyrosine residues serve as docking sites for intracellular proteins, such as Grb2 and SOS, which have SH2 domains. Ras is activated by the exchange of GDP for GTP. Ras-GTP (active form) activates the serine/threonine kinase Raf, initiating a phosphorylation cascade that results in the activation of MAP kinase. MAP ki-nase translocates to the nucleus and phosphorylates transcription factors to modulate gene transcription.

One of these signaling pathways includes the activation of another GTPase that is related to the trimeric G proteins. Members of the ras family of monomeric G proteins are activated by many tyrosine kinase receptor growth factor agonists and, in turn, activate an intracellular signaling cascade that involves the phosphorylation and activation of several protein kinases called mitogen-activated protein kinases (MAP kinases). Activated MAP kinase translocates to the nucleus, where it activates the transcription of genes involved in the transcription of other genes, the immediate early genes.

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