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

Research output: Contribution to journalArticle

97 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number5 44-5
StatePublished - Dec 5 1998

Fingerprint

Non-Receptor Type 6 Protein Tyrosine Phosphatase
Phosphorylation
Angiotensin II
Tyrosine
Janus Kinases
Association reactions
Transcription
Transducers
Phosphoric Monoester Hydrolases
Chemical activation
Electroporation
Cell proliferation
G-Protein-Coupled Receptors
Complexation
Vascular Smooth Muscle
GTP-Binding Proteins
Smooth Muscle Myocytes
Muscle
Cells
Cell Proliferation

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).

Regulation of angiotensin II-induced JAK2 tyrosine phosphorylation : Roles of SHP-1 and SHP-2. / Marrero, Mario B; Venema, Virginia J.; Ju, Hong; Eaton, Douglas C.; Venema, Richard C.

In: American Journal of Physiology - Cell Physiology, Vol. 275, No. 5 44-5, 05.12.1998.

Research output: Contribution to journalArticle

Marrero, Mario B ; Venema, Virginia J. ; Ju, Hong ; Eaton, Douglas C. ; Venema, Richard C. / Regulation of angiotensin II-induced JAK2 tyrosine phosphorylation : Roles of SHP-1 and SHP-2. In: American Journal of Physiology - Cell Physiology. 1998 ; Vol. 275, No. 5 44-5.
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