Receptor biology

Antagonism in the family

Science's STKE  28 Sep 1999:
Vol. 1999, Issue 1, pp. tw7
DOI: 10.1126/stke.1999.1.tw7

The receptor tyrosine kinase p185HER-2 is implicated in several human carcinomas. When overexpressed, this receptor dimerizes in the absence of a known ligand and becomes constitutively activated. This receptor can also heterodimerize with ligand-activated members of the structurally related epidermal growth factor receptor family. Doherty et al. have identified a naturally occurring inhibitor of p185HER-2 called herstatin. This secreted protein is the product of an alternatively spliced HER-2 transcript that encodes part of the receptor extracellular domain as well as residues encoded by an intron. By binding to p185HER-2, herstatin may inhibit receptor dimerization. Hence, herstatin may have value as a growth inhibitor in anti-cancer therapies.

Doherty, J.K., Bond, C., Jardim, A., Adelman, J.P., Clinton, G.M. (1999) The HER-2/neu receptor tyrosine kinase gene encodes a secreted autoinhibitor. Proc. Natl. Acad. Sci. U.S.A. 96: 10869-10874. [Abstract] [Full Text]