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 (AI1A) The AT1A, receptor is a member of ihe (J-protem coupled receptor superfamily has hceii blumn to activate the AT1A. 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 AT1A, receptor (AT1A306-358 physically associate with Jak2 in an angiotensin II dependent manner. Dektion mutants of the cvtoplasmic domain of the AT1A 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 AT1A-Jak2 interaction1; that surest a unique signaling mechanisms for G-protein coupled receptors that is -imilarto cytokme and growth factor receptors.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology