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This term refers to the phosphorylation, i.e., the transfer of phosphate groups, to amino acids within a protein possessing the activity of a protein kinase such as in many receptors for cytokines (see also: PTK; protein tyrosine kinase).
Autophosphorylation reactions are observed frequently following the binding of a ligand to a receptor with intrinsic protein kinase activity. The binding of a ligand first induces the formation of receptor dimers. An autophosphorylation therefore is really a transphosphorylation reaction in which one receptor subunit of the dimer phosphorylates the other subunit. The induction of tyrosine phosphorylation is usually transient and returns to basal level within 20 to 30 minutes. Dephosphorylation is mediated by (specific) protein tyrosine phosphatases (see, for example: HCP). It has been observed that inhibitors of such phosphatases can transiently substitute for growth factors and induce a mitogenic response (see: Okadaic acid).
The majority of the receptors for hematopoietins (Hematopoietic growth factors) do not possess intrinsic tyrosine kinase activity in their intracellular domain. These receptors have been shown to become phosphorylated by other proteins (see, for example: lck, Janus kinases) that interact with the intracellular domains of such receptors via src homology domains. In addition, ligand binding to such receptors also leads to the phosphorylation of other cellular substrate molecules.
Autophosphorylation reactions appear to play an important role in the regulation of the biological activities of many cytokine receptors (see also: Cytokine receptor families). It has been observed that the intrinsic protein kinase activity of these receptors is enhanced significantly after having become phosphorylated. If the process of receptor phosphorylation is blocked by suitable inhibitors, receptor mediated biological responses are usually also blocked. A critical role for tyrosine phosphorylation in growth regulation is suggested by the observation that inhibitors of tyrosine kinases inhibit cell growth, that inhibitors of tyrosine phosphatases can stimulate cell proliferation in the absence of a suitable receptor ligand and that mutant receptors show a direct correlation between the ability to induce tyrosine phosphorylation and the ability to support ligand induced cell growth.
Compounds that have been described to block receptor phosphorylation and other phosphorylation reactions include Genistein, H8, Herbimycin A, Lavendustin A, Staurosporine, Suramin and Tyrphostins.
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