Regulation of angiotensin II-induced JAK2 tyrosine phosphorylation: Roles of SHP-1 and SHP-2

Mario B. Marrero, Virginia J. Venema, Hong Ju, Douglas C. Eaton, Richard C. Venema

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Abstract

Angiotensin II (ANG II) exerts its effects on vascular smooth muscle cells through G protein-coupled AT1 receptors. ANG II stimulation activates the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway by inducing tyrosine phosphorylation, activation, and association of JAK2 with the receptor. Association appears to be required for JAK2 phosphorylation. In the present study, electroporation experiments with neutralizing anti-Src homology phosphatase-1 (SHP-1) and antiSHP-2 antibodies and time course determinations of SHP-1 and SHP-2 activation and complexation with JAK2 suggest that the tyrosine phosphatases, SHP-1 and SHP-2, have opposite roles in ANG II-induced JAK2 phosphorylation. SHP-1 appears responsible for JAK2 dephosphorylation and termination of the ANG II-induced JAK/STAT cascade. SHP-2 appears to have an essential role in JAK2 phosphorylation and initiation of the ANG II-induced JAK/STAT cascade leading to cell proliferation. The motif in the AT1 receptor that is required for association with JAK2 is also required for association with SHP-2. Furthermore, SHP-2 is required for JAK2-receptor association. SHP-2 may thus play a role as an adaptor protein for JAK2 association with the receptor, thereby facilitating JAK2 phosphorylation and activation.

Original languageEnglish (US)
Pages (from-to)C1216-C1223
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number5 44-5
Publication statusPublished - Dec 5 1998

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Keywords

  • Adaptor protein
  • Tyrosine phosphatases
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Marrero, M. B., Venema, V. J., Ju, H., Eaton, D. C., & Venema, R. C. (1998). Regulation of angiotensin II-induced JAK2 tyrosine phosphorylation: Roles of SHP-1 and SHP-2. American Journal of Physiology - Cell Physiology, 275(5 44-5), C1216-C1223.