ANGIOTENSIN-II-INDUCED ASSOCIATION OF PHOSPHOLIPASE-C-GAMMA-1 WITH THE G-PROTEIN-COUPLED AT(1)-RECEPTOR

An early event in signaling by the G-protein-coupled angiotensin II (A ng II) AT(1) receptor in vascular smooth muscle cells is the tyrosine phosphorylation and activation of phospholipase C gamma 1 (PLC gamma 1 ). In the present study, we show that stimulation of this event by Ang II in vascular smooth muscle cells is accompanied by binding of PLC g amma 1 to the AT(1) receptor in an Ang II- and tyrosine phosphorylatio n-dependent manner. The PLC gamma 1-AT(1), receptor interaction appear s to depend on phosphorylation of tyrosine 319 in a YIPP motif in the C-terminal intracellular domain of the AT(1) receptor and binding of t he phosphorylated receptor by the most C-terminal of two Src homology 2 domains in PLC gamma 1. PLC gamma 1 thus binds to the same site in t he receptor previously identified for binding by the SHP-2 phosphotyro sine phosphatase-JAK2 tyrosine kinase complex. A single site in the C- terminal tail of the AT(1) receptor can, therefore, be bound in a liga nd-independent manner by two different downstream effector proteins. T hese 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 obse rved for classic growth factor receptors.