Angiotensin II signalling events mediated by tyrosine phosphorylation.
Angiotensin II is a potent vasoconstrictor that is important in the control of systemic blood pressure. All the hemodynamic effects of angiotensin II result from the AT1 receptor which has the structural features of a seven transmembrane receptor. Both in cultured rat aortic smooth muscle cells and rat glomerular mesangial cells, angiotensin II stimulates the rapid tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1). Tyrosine kinase inhibitors that block this phosphorylation also block the angiotensin II-mediated production of 1,4,5 inositol trisphosphate (1,4,5-IP3) and the intracellular release of Ca2+. The cellular tyrosine kinase c-src appears to play a critical role in the angiotensin II-stimulated tyrosine phosphorylation of PLC-gamma 1 and the generation of 1,4,5-IP3. We have also found that angiotensin II stimulates the tyrosine phosphorylation and activation of the JAK family of intracellular kinases. This in turn activates the STAT family of transcription factors. Angiotensin II, working through the AT1 receptor, uses tyrosine phosphorylation as a mechanism to convey signals from the cell surface to the cell nucleus.
Marrero
M B
MB
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
Paxton
W G
WG
Schieffer
B
B
Ling
B N
BN
Bernstein
K E
KE
D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008958:Models, Molecular; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D011945:Receptors, Angiotensin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507906:Jak1 protein, rat; C507927:Jak2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D010738:Type C Phospholipases; D051966:Phospholipase C gamma