Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: Identification of a c-Src/Cav-1/Grb7 signaling cassette

H. Lee, D. Volonte, F. Galbiati, P. Iyengar, D. M. Lublin, D. B. Bregman, M. T. Wilson, R. Campos-Gonzalez, B. Bouzahzah, R. G. Pestell, P. E. Scherer, M. P. Lisanti

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Abstract

Caveolin-1 was first identified as a phosphoprotein in Rous sarcoma virus (RSV)-transformed chicken embryo fibroblasts. Tyrosine 14 is now thought to be the principal site for recognition by c-Src kinase; however, little is known about this phosphorylation event. Here, we generated a monoclonal antibody (mAb) probe that recognizes only tyrosine 14-phosphorylated caveolin-1. Using this approach, we show that caveolin-1 (Y14) is a specific tyrosine kinase substrate that is constitutively phosphorylated in Src- and Abl-transformed cells and transiently phosphorylated in a regulated fashion during growth factor signaling. We also provide evidence that tyrosine-phosphorylated caveolin-1 is localized at the major sites of tyrosine-kinase signaling, i.e. focal adhesions. By analogy with other signaling events, we hypothesized that caveolin-1 could serve as a docking site for pTyr-binding molecules. In support of this hypothesis, we show that phosphorylation of caveolin-1 on tyrosine 14 confers binding to Grb7 (an SH2-domain containing protein) both in vitro and in vivo. Furthermore, we demonstrate that binding of Grb7 to tyrosine 14-phosphorylated caveolin-1 functionally augments anchorage-independent growth and epidermal growth factor (EGF)-stimulated cell migration. We discuss the possible implications of our findings in the context of signal transduction.

Original languageEnglish (US)
Pages (from-to)1750-1775
Number of pages26
JournalMolecular Endocrinology
Volume14
Issue number11
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Lee, H., Volonte, D., Galbiati, F., Iyengar, P., Lublin, D. M., Bregman, D. B., Wilson, M. T., Campos-Gonzalez, R., Bouzahzah, B., Pestell, R. G., Scherer, P. E., & Lisanti, M. P. (2000). Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: Identification of a c-Src/Cav-1/Grb7 signaling cassette. Molecular Endocrinology, 14(11), 1750-1775. https://doi.org/10.1210/mend.14.11.0553