Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor

M. Showkat Ali, Peter P. Sayeski, Laurie B. Dirksen, David J. Hayzer, Mario B Marrero, Kenneth E. Bernstein

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Abstract

Angiotensin II is the effector molecule of the reninangiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-proteincoupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT(1A) receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT(1A) receptor motif YIPP (amino acids 319-322). The wild-type AT(1A) receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT(1A) receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT(1A) receptor. The binding of the AT(1A) receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.

Original languageEnglish (US)
Pages (from-to)23382-23388
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number37
DOIs
Publication statusPublished - Sep 26 1997

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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