Hyperglycemia enhances angiotensin II-induced janus-activated kinase/STAT signaling in vascular smooth muscle cells

Farhad Amiri, Virginia J. Venema, Xiaodan Wang, Hong Ju, Richard C Venema, Mario B Marrero

Research output: Contribution to journalArticle

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Abstract

We have shown previously that angiotensin II (Ang II) activates the janus-activated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in vascular smooth muscle cells (VSMCs) and that activation of the JAK/STAT pathway is required for Ang II induction of VSMC proliferation. In the present study, we examined the effects of hyperglycemia (HG) on Ang II-induced JAK/STAT signaling events in cultured VSMCs. HG increases Ang II-induced JAK2 tyrosine phosphorylation and promotes a partial tyrosine phosphorylation of the enzyme under basal conditions. In addition, HG increases both basal and Ang II-induced complex formation of JAK2 with the Ang II AT1 receptor. The extent of STAT1 and STAT3 tyrosine and serine phosphorylation are also increased under HG conditions. Furthermore, the tyrosine phosphorylation and activities of the SHP-1 and SHP-2 tyrosine phosphatases, enzymes that regulate Ang II-induced JAK2 tyrosine phosphorylation, are altered by HG. SHP-1, which is responsible for JAK2 tyrosine dephosphorylation in VSMC, is completely deactivated in HG, resulting in a prolonged duration of JAK2 phosphorylation under HG conditions. HG also enhances Ang II induction of VSMC proliferation. Taken together, these data suggest that HG augments Ang II induction of VSMC proliferation by increasing signal transduction through the JAK/STAT pathway.

Original languageEnglish (US)
Pages (from-to)32382-32386
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number45
DOIs
StatePublished - Nov 5 1999

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Janus Kinases
Transcription
Transducers
Vascular Smooth Muscle
Angiotensin II
Hyperglycemia
Smooth Muscle Myocytes
Muscle
Phosphorylation
Phosphotransferases
Cells
Tyrosine
Cell proliferation
Cell Proliferation
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Signal transduction
Angiotensin Type 1 Receptor
Angiotensin Receptors
Enzymes
Phosphoric Monoester Hydrolases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hyperglycemia enhances angiotensin II-induced janus-activated kinase/STAT signaling in vascular smooth muscle cells. / Amiri, Farhad; Venema, Virginia J.; Wang, Xiaodan; Ju, Hong; Venema, Richard C; Marrero, Mario B.

In: Journal of Biological Chemistry, Vol. 274, No. 45, 05.11.1999, p. 32382-32386.

Research output: Contribution to journalArticle

Amiri, Farhad ; Venema, Virginia J. ; Wang, Xiaodan ; Ju, Hong ; Venema, Richard C ; Marrero, Mario B. / Hyperglycemia enhances angiotensin II-induced janus-activated kinase/STAT signaling in vascular smooth muscle cells. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 45. pp. 32382-32386.
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