An essential role of the Jak-2/STAT-3/cytosolic phospholipase A2 axis in platelet-derived growth factor BB-induced vascular smooth muscle cell motility

Indira Neeli, Zhimin Liu, Nagadhara Dronadula, Z. Alex Ma, Rao Gadiparthi

Research output: Contribution to journalArticle

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Abstract

Platelet-derived growth factor-BB (PDGF-BB) is a potent motogen for vascular smooth muscle cells (VSMCs). To understand its motogenic signaling events, we have studied the role of the Janus-activated kinase/signal transducers and activators of transcription (Jak/STAT) pathway and cytosolic phospholipase A2 (CPLA2). PDGF-BB stimulated tyrosine phosphorylation of Jak-2 and STAT-3 in a time-dependent manner in VSMCs. In addition, AG490 and Jak-2KEpRK5, a selective pharmacological inhibitor and a dominant negative mutant, respectively, of Jak-2, attenuated PDGF-BB-induced STAT-3 tyrosine phosphorylation and its DNA binding and reporter gene activities. PDGF-BB induced VSMC motility in a dose-dependent manner with a maximum effect at 10 ng/ml. Dominant negative mutant-dependent suppression of Jak-2 and STAT-3 blocked PDGF-BB-induced VSMC motility. PDGF-BB induced the expression of CPLA2 in a Jak-2/STAT-3-dependent manner, and pharmacological inhibitors of CPLA2 prevented PDGF-BB-induced VSMC motility. Furthermore, either exogenous addition of arachidonic acid or forced expression of CPLA2 rescued PDGF-BB-induced VSMC motility from inhibition by blockade of Jak-2 and STAT-3 activation. Together, these results for the first time show that PDGF-BB-induced VSMC motility requires activation of the Jak-2/STAT-3/cPLA2 signaling axis.

Original languageEnglish (US)
Pages (from-to)46122-46128
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number44
DOIs
StatePublished - Oct 29 2004

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Cytosolic Phospholipases A2
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Movement
Muscle
Cells
Phosphorylation
Chemical activation
Pharmacology
Janus Kinases
platelet-derived growth factor BB
Transcription
Transducers
Reporter Genes
Arachidonic Acid
Tyrosine
Phosphotransferases
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

An essential role of the Jak-2/STAT-3/cytosolic phospholipase A2 axis in platelet-derived growth factor BB-induced vascular smooth muscle cell motility. / Neeli, Indira; Liu, Zhimin; Dronadula, Nagadhara; Ma, Z. Alex; Gadiparthi, Rao.

In: Journal of Biological Chemistry, Vol. 279, No. 44, 29.10.2004, p. 46122-46128.

Research output: Contribution to journalArticle

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