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

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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

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Neuregulin-1
Phosphorylation
Fibroblasts
Epidermal Growth Factor
Tyrosine
Genes
Ligands
Receptor Protein-Tyrosine Kinases
Epidermal Growth Factor Receptor
Intercellular Signaling Peptides and Proteins
Antibodies
Insects
Proteins
histidine-rich proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

The erbB3 gene product is a receptor for heregulin. / Carraway, Kermit L; Sliwkowski, Mark X.; Akita, Robert; Platko, Jill V.; Guy, Pamela M.; Nuijens, Andrew; John Diamonti, A.; Vandlen, Richard L.; Cantley, Lewis C.; Cerione, Richard A.

In: Journal of Biological Chemistry, Vol. 269, No. 19, 13.05.1994, p. 14303-14306.

Research output: Contribution to journalArticle

Carraway, KL, Sliwkowski, MX, Akita, R, Platko, JV, Guy, PM, Nuijens, A, John Diamonti, A, Vandlen, RL, Cantley, LC & Cerione, RA 1994, 'The erbB3 gene product is a receptor for heregulin', Journal of Biological Chemistry, vol. 269, no. 19, pp. 14303-14306.
Carraway KL, Sliwkowski MX, Akita R, Platko JV, Guy PM, Nuijens A et al. The erbB3 gene product is a receptor for heregulin. Journal of Biological Chemistry. 1994 May 13;269(19):14303-14306.
Carraway, Kermit L ; Sliwkowski, Mark X. ; Akita, Robert ; Platko, Jill V. ; Guy, Pamela M. ; Nuijens, Andrew ; John Diamonti, A. ; Vandlen, Richard L. ; Cantley, Lewis C. ; Cerione, Richard A. / The erbB3 gene product is a receptor for heregulin. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 19. pp. 14303-14306.
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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.",
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