Mappinc. The cviotiasmic domain of thf, ati typf ia rfc fptorforjak2 rinding

Angiotensin II is (he major effector molecule of the renin-angiotensin system. Virtually nil o! if, physiological actions me mediated h\ the type 1A angiotensin II receptor (AI_1A) The AT_1A, receptor is a member of ihe (J-protem coupled receptor superfamily has hceii blumn to activate the AT_1A. receplur associated t>rusine kinase Jak2 (Nature 375:247-250] The presaH studs represenl-. .in initial effort io identify the cyloplasmic rcuinri of the receptor t hut iu critical for Jak2 association and activation Here, we demonstrate th.it a (iST-fusion protein containing the terminal 54 amino acids of the cNloplasmic domain of the AT_1A, receptor (AT_1A306-358 physically associate with Jak2 in an angiotensin II dependent manner. Dektion mutants of the cvtoplasmic domain of the AT_1A receptor were used to determine the region that is critical for association of Jak2. Mutant-, lacking the YIPP motif corresponding to residues 31° to 322 failed to mediate Jak2 precipilabiliu hoth in vitro and in vivo Competition experiments with wild type and mutant synthetic pep!ides corresponding to the YIPP motif of the receptor further t on firmed these results. ! aken together, these studies identified a novel sequences that mediate AT_1A-Jak2 interaction1; that surest a unique signaling mechanisms for G-protein coupled receptors that is -imilarto cytokme and growth factor receptors.