Cytosolic phospholipase A2 is an effector of Jak/STAT signaling and is involved in platelet-derived growth factor BB-induced growth in vascular smooth muscle cells

Chandrahasa R. Yellaturu, Rao Gadiparthi

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for vascular smooth muscle cells (VSMC). To understand its mitogenic and chemotactic signaling events, we studied the role of cytosolic phospholipase A2 (cPLA2) and the Jak/STAT pathway. PDGF-BB induced the expression and activity of cPLA2 in a time-dependent manner in VSMC. Arachidonyl trifluoromethyl ketone, a potent and specific inhibitor of cPLA2, significantly reduced PDGF-BB-induced arachidonic acid release and DNA synthesis. PDGF-BB stimulated tyrosine phosphorylation of Jak-2 in a time-dependent manner. In addition, PDGF-BB activated STAT-3 as determined by its tyrosine phosphorylation, DNA-binding activity, and reporter gene expression, and these responses were suppressed by AG490, a selective inhibitor of Jak-2. AG490 and a dominant-negative mutant of STAT-3 also attenuated PDGF-BB-induced expression of cPLA2, arachidonic acid release, and DNA synthesis in VSMC. Together, these results suggest that induction of expression of cPLA2 and arachidonic acid release are involved in VSMC growth in response to PDGF-BB and that these events are mediated by Jak-2-dependent STAT-3 activation.

Original languageEnglish (US)
Pages (from-to)9986-9992
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number11
DOIs
StatePublished - Mar 14 2003

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Cytosolic Phospholipases A2
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Cells
Growth
Arachidonic Acid
Phosphorylation
Tyrosine
DNA
Chemotactic Factors
Cell growth
platelet-derived growth factor BB
Reporter Genes
Mitogens
Gene expression
Chemical activation
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

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title = "Cytosolic phospholipase A2 is an effector of Jak/STAT signaling and is involved in platelet-derived growth factor BB-induced growth in vascular smooth muscle cells",
abstract = "Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for vascular smooth muscle cells (VSMC). To understand its mitogenic and chemotactic signaling events, we studied the role of cytosolic phospholipase A2 (cPLA2) and the Jak/STAT pathway. PDGF-BB induced the expression and activity of cPLA2 in a time-dependent manner in VSMC. Arachidonyl trifluoromethyl ketone, a potent and specific inhibitor of cPLA2, significantly reduced PDGF-BB-induced arachidonic acid release and DNA synthesis. PDGF-BB stimulated tyrosine phosphorylation of Jak-2 in a time-dependent manner. In addition, PDGF-BB activated STAT-3 as determined by its tyrosine phosphorylation, DNA-binding activity, and reporter gene expression, and these responses were suppressed by AG490, a selective inhibitor of Jak-2. AG490 and a dominant-negative mutant of STAT-3 also attenuated PDGF-BB-induced expression of cPLA2, arachidonic acid release, and DNA synthesis in VSMC. Together, these results suggest that induction of expression of cPLA2 and arachidonic acid release are involved in VSMC growth in response to PDGF-BB and that these events are mediated by Jak-2-dependent STAT-3 activation.",
author = "Yellaturu, {Chandrahasa R.} and Rao Gadiparthi",
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AU - Yellaturu, Chandrahasa R.

AU - Gadiparthi, Rao

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N2 - Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for vascular smooth muscle cells (VSMC). To understand its mitogenic and chemotactic signaling events, we studied the role of cytosolic phospholipase A2 (cPLA2) and the Jak/STAT pathway. PDGF-BB induced the expression and activity of cPLA2 in a time-dependent manner in VSMC. Arachidonyl trifluoromethyl ketone, a potent and specific inhibitor of cPLA2, significantly reduced PDGF-BB-induced arachidonic acid release and DNA synthesis. PDGF-BB stimulated tyrosine phosphorylation of Jak-2 in a time-dependent manner. In addition, PDGF-BB activated STAT-3 as determined by its tyrosine phosphorylation, DNA-binding activity, and reporter gene expression, and these responses were suppressed by AG490, a selective inhibitor of Jak-2. AG490 and a dominant-negative mutant of STAT-3 also attenuated PDGF-BB-induced expression of cPLA2, arachidonic acid release, and DNA synthesis in VSMC. Together, these results suggest that induction of expression of cPLA2 and arachidonic acid release are involved in VSMC growth in response to PDGF-BB and that these events are mediated by Jak-2-dependent STAT-3 activation.

AB - Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for vascular smooth muscle cells (VSMC). To understand its mitogenic and chemotactic signaling events, we studied the role of cytosolic phospholipase A2 (cPLA2) and the Jak/STAT pathway. PDGF-BB induced the expression and activity of cPLA2 in a time-dependent manner in VSMC. Arachidonyl trifluoromethyl ketone, a potent and specific inhibitor of cPLA2, significantly reduced PDGF-BB-induced arachidonic acid release and DNA synthesis. PDGF-BB stimulated tyrosine phosphorylation of Jak-2 in a time-dependent manner. In addition, PDGF-BB activated STAT-3 as determined by its tyrosine phosphorylation, DNA-binding activity, and reporter gene expression, and these responses were suppressed by AG490, a selective inhibitor of Jak-2. AG490 and a dominant-negative mutant of STAT-3 also attenuated PDGF-BB-induced expression of cPLA2, arachidonic acid release, and DNA synthesis in VSMC. Together, these results suggest that induction of expression of cPLA2 and arachidonic acid release are involved in VSMC growth in response to PDGF-BB and that these events are mediated by Jak-2-dependent STAT-3 activation.

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