Angiotensin II-induced association of phospholipase Cγ1 with the G- protein-coupled AT1 receptor

Richard C Venema, Hong Ju, Virginia J. Venema, Bernhard Schieffer, Joyce B. Harp, Brian N. Ling, Douglas C. Eaton, Mario B Marrero

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Abstract

An early event in signaling by the G-protein-coupled angiotensin II (Ang II) AT1 receptor in vascular smooth muscle cells is the tyrosine phosphorylation and activation of phospholipase Cγ1 (PLCγ1). In the present study, we show that stimulation of this event by Ang II in vascular smooth muscle cells is accompanied by binding of PLCγ1 to the AT1 receptor in an AngII- and tyrosine phosphorylation-dependent manner. The PLCγ-AT1 receptor interaction appears to depend on phosphorylation of tyrosine 319 in a YIPP motif in the C-terminal intracellular domain of the AT1 receptor and binding of the phosphorylated receptor by the most C-terminal of two Src homology 2 domains in PLCγ1. PLCγ1 thus binds to the same site in the receptor previously identified for binding by the SHP-2 phosphotyrosine phosphatase- JAK2 tyrosine kinase complex. A single site in the C-terminal tail of the AT1 receptor can, therefore, be bound in a ligand-dependent manner by two different downstream effector proteins. These data demonstrate that G- protein-coupled receptors can physically associate with intracellular proteins other than G proteins, creating membrane-delimited signal transduction complexes similar to those observed for classic growth factor receptors.

Original languageEnglish (US)
Pages (from-to)7703-7708
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number13
DOIs
StatePublished - Mar 27 1998

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Venema, R. C., Ju, H., Venema, V. J., Schieffer, B., Harp, J. B., Ling, B. N., Eaton, D. C., & Marrero, M. B. (1998). Angiotensin II-induced association of phospholipase Cγ1 with the G- protein-coupled AT1 receptor. Journal of Biological Chemistry, 273(13), 7703-7708. https://doi.org/10.1074/jbc.273.13.7703