Identification of autophosphorylation sites of HER2/neu.

Rachel Hazan, B. Margolis, M. Dombalagian, A. Ullrich, A. Zilberstein, J. Schlessinger

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

HER2 or c-erbB-2 is a putative growth factor receptor with sequence homology to the epidermal growth factor receptor. It is the human homologue of the rat protooncogene neu and may have an important role in human malignancies such as breast and ovarian cancers. Like other growth factor receptors, HER2 has intrinsic protein tyrosine kinase activity and undergoes autophosphorylation. Recently, we have demonstrated that, similar to the epidermal growth factor receptor, all autophosphorylation sites of HER2 are localized in the carboxyl terminus of this protein. In the present study, immunopurified HER2 was allowed to autophosphorylate, and tryptic phosphopeptides were generated. After purification of these phosphopeptides by high performance liquid chromatography, microsequencing was performed. Utilizing this approach, two autophosphorylation sites were unequivocally identified at Y1023 and Y1248. The sequences of two other tyrosine phosphorylated tryptic peptides were determined, but the exact site of autophosphorylation could not be determined because multiple tyrosines were located on each peptide. However, each of these peptides contains tyrosines that correspond to major autophosphorylation sites of the epidermal growth factor receptor, suggesting that, in addition to Y1023 and Y1248, Y1139 and Y1222 also serve as autophosphorylation sites of HER2.

Original languageEnglish (US)
Pages (from-to)3-7
Number of pages5
JournalCell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
Volume1
Issue number1
StatePublished - Jan 1990
Externally publishedYes

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Epidermal Growth Factor Receptor
Tyrosine
Phosphopeptides
Growth Factor Receptors
Peptides
Sequence Homology
Ovarian Neoplasms
Protein-Tyrosine Kinases
High Pressure Liquid Chromatography
Breast Neoplasms
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Identification of autophosphorylation sites of HER2/neu. / Hazan, Rachel; Margolis, B.; Dombalagian, M.; Ullrich, A.; Zilberstein, A.; Schlessinger, J.

In: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, Vol. 1, No. 1, 01.1990, p. 3-7.

Research output: Contribution to journalArticle

Hazan, Rachel ; Margolis, B. ; Dombalagian, M. ; Ullrich, A. ; Zilberstein, A. ; Schlessinger, J. / Identification of autophosphorylation sites of HER2/neu. In: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1990 ; Vol. 1, No. 1. pp. 3-7.
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