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Receptors: Making the Tag

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Science's STKE  12 Oct 1999:
Vol. 1999, Issue 3, pp. tw7
DOI: 10.1126/stke.1999.3.tw7

Receptor protein-tyrosine kinases are activated in response to binding of extracellular ligands and control many biological processes. Just as proper cellular regulation requires finely controlled activation of such receptors, the termination of such signals must be tightly controlled. The degradation of many key signaling proteins is controlled by covalent attachment of the small protein ubiquitin, which targets the protein for degradation. The protein c-Cbl associates with activated receptors such as the platelet-derived growth factor receptor or epidermal growth factor receptor and leads to ubiquitination and degradation of the receptor. Joazeiro et al. report that c-Cbl is itself a ubiquitin-protein ligase or E3 enzyme. The c-Cbl protein was shown to promote transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to substrate proteins.

Joazeiro, C.A.P., Wing, S.S., Huang, H.-K., Leverson, J.D., Hunter, T., and Liu, Y.-C. (1999) The tyrosine kinase negative regulator c-Cbl as a RING-Type, E2-dependent ubiquitin-protein ligase. Science 286: 309-312. [Abstract] [Full Text]

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