The erbB3 gene product is a receptor for heregulin

Kermit L Carraway, Mark X. Sliwkowski, Robert Akita, Jill V. Platko, Pamela M. Guy, Andrew Nuijens, A. John Diamonti, Richard L. Vandlen, Lewis C. Cantley, Richard A. Cerione

Research output: Contribution to journalArticle

321 Scopus citations

Abstract

ErbB3 is a member of the epidermal growth factor (EGF) receptor subfamily of receptor tyrosine kinases and is believed to be a receptor for an unknown ligand. We have tested the possibility that heregulin, a growth factor possessing an EGF-like domain, is a ligand for ErbB3. We have found that the iodinated recombinant EGF-like domain of heregulin-β1 (125I- rHRGβ1177-244) bound specifically to insect cell-expressed bovine ErbB3 with a dissociation constant of 0.85 nM. Moreover, 125I- rHRGβ1177-244 bound to NIH3T3 fibroblasts stably transfected with bovine erbB3 with a dissociation constant of 60 pM, but did not bind to parental cells. 125I-rHRGβ1177-244 could be chemically cross- linked to a 170-180 kDa protein in erbB3-transfected fibroblasts, and the cross-linked product could be immunoprecipitated with antibodies specific for ErbB3. Finally, rHRGβ1 stimulated the tyrosine phosphorylation of both ErbB3 and endogenous p185(erbB2/neu) in transfectants but not in parental cells. We conclude that ErbB3 is a receptor for HRG and is capable of mediating HRG- stimulated tyrosine phosphorylation of itself and p185(erbB2/neu) in cells that express both receptors.

Original languageEnglish (US)
Pages (from-to)14303-14306
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number19
StatePublished - May 13 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Carraway, K. L., Sliwkowski, M. X., Akita, R., Platko, J. V., Guy, P. M., Nuijens, A., John Diamonti, A., Vandlen, R. L., Cantley, L. C., & Cerione, R. A. (1994). The erbB3 gene product is a receptor for heregulin. Journal of Biological Chemistry, 269(19), 14303-14306.