Angiotensin II-induced tyrosine phosphorylation of signal transducers and activators of transcription 1 is regulated by janus-activated kinase 2 and Fyn kinases and mitogen-activated protein kinase phosphatase 1

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

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Abstract

Angiotensin II (Ang H) AT1 receptors on vascular smooth muscle cells (VSMCs) are coupled to the Janus-activated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. We have shown previously that Ang II stimulation of VSMCs results in the tyrosine phosphorylation of JAK2 and STAT1 and the translocation of STAT1 to the nucleus. In the present study, we demonstrate using specific enzyme inhibitors and antisense oligonucleotides that both JAK2 and p59 Fyn tyrosine kinases are required for the Ang II-induced tyrosine phosphorylation and nuclear translocation of STAT1 in VSMCs. Neither tyrosine kinase, however, appears to function upstream from the other in a phosphorylation cascade. Rather, p59 Fyn functions as an Ang II-activated docking protein for both JAK2 and STAT1, a docking interaction that may facilitate JAK2-mediated STAT1 tyrosine phosphorylation. In this study, we have also identified the nuclear dual- specificity phosphatase mitogen-activated protein kinase phosphatase 1 as the enzyme responsible for STAT1 tyrosine dephosphorylation in VSMCs.

Original languageEnglish (US)
Pages (from-to)30795-30800
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number46
DOIs
StatePublished - Nov 13 1998

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Mitogen-Activated Protein Kinase Phosphatases
Dual Specificity Phosphatase 1
MAP Kinase Kinase 1
Janus Kinase 2
STAT1 Transcription Factor
Phosphorylation
Vascular Smooth Muscle
Angiotensin II
Smooth Muscle Myocytes
Tyrosine
Muscle
Phosphotransferases
Proto-Oncogene Proteins c-fyn
Dual-Specificity Phosphatases
Janus Kinases
Antisense Oligonucleotides
Enzyme Inhibitors
Transcription
Transducers
Protein-Tyrosine Kinases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Angiotensin II-induced tyrosine phosphorylation of signal transducers and activators of transcription 1 is regulated by janus-activated kinase 2 and Fyn kinases and mitogen-activated protein kinase phosphatase 1. / Venema, Richard C.; Venema, Virginia J.; Eaton, Douglas C.; Marrero, Mario B.

In: Journal of Biological Chemistry, Vol. 273, No. 46, 13.11.1998, p. 30795-30800.

Research output: Contribution to journalArticle

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abstract = "Angiotensin II (Ang H) AT1 receptors on vascular smooth muscle cells (VSMCs) are coupled to the Janus-activated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. We have shown previously that Ang II stimulation of VSMCs results in the tyrosine phosphorylation of JAK2 and STAT1 and the translocation of STAT1 to the nucleus. In the present study, we demonstrate using specific enzyme inhibitors and antisense oligonucleotides that both JAK2 and p59 Fyn tyrosine kinases are required for the Ang II-induced tyrosine phosphorylation and nuclear translocation of STAT1 in VSMCs. Neither tyrosine kinase, however, appears to function upstream from the other in a phosphorylation cascade. Rather, p59 Fyn functions as an Ang II-activated docking protein for both JAK2 and STAT1, a docking interaction that may facilitate JAK2-mediated STAT1 tyrosine phosphorylation. In this study, we have also identified the nuclear dual- specificity phosphatase mitogen-activated protein kinase phosphatase 1 as the enzyme responsible for STAT1 tyrosine dephosphorylation in VSMCs.",
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