The role of tyrosine phosphorylation in angiotensin II mediated intracellular signaling and cell growth

B. Schieffer, K. E. Bernstein, M. B. Marrero

Research output: Contribution to journalReview article

37 Scopus citations

Abstract

Most cell types, including vascular smooth muscle cells and rat kidney mesangial cells, are controlled mainly by two types of cell surface receptors: (a) single membrane-spanning tyrosine kinase receptors for growth factors and (b) seven-transmembrane G-protein linked receptors for vasoactive peptides such as angiotensin II, vasopressin, and endothelin. These vasoactive peptide hormones also act as growth factors in normal and abnormal cell development. However, in contrast to the growth factor receptors (e.g., epidermal growth factor receptor and platelet-derived growth factor receptor), the G-protein linked receptors, such as the angiotensin II AT1 receptor, lack cytoplasmic tyrosine kinase domains. Nevertheless, angiotensin II has recently been demonstrated to cause increased tyrosine phosphorylation of numerous proteins in several cellular systems. For example, angiotensin II has been reported to induce the tyrosine phosphorylation of the γ-isoform of phospholipase C, pp120, pp125(FAK), and members of the janus kinase/signal transducer and activator of transcription pathway. Furthermore, angiotensin II seems to modulate the activity of the soluble cytoplasmic tyrosine kinase pp60(c-src), and this tyrosine kinase has been implicated in the phosphorylation of some of the above proteins. Understanding the biochemistry of tyrosine phosphorylation involved in G-protein coupled receptors, such as the AT1 receptor, may therefore lead to the development of new pharmacological interventions important in cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)85-91
Number of pages7
JournalJournal of Molecular Medicine
Volume74
Issue number2
DOIs
StatePublished - Jan 1 1996

Keywords

  • Angiotensin II
  • Angiotensin II type 1 receptor
  • Janus kinase/signal transducers and activators of transcription pathway
  • Phospholipase C
  • src kinase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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