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.
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 A(2) (cPLA(2)) and the Jak/STAT pathway. PDGF-BB induced the expression and activity of cPLA(2) in a time-dependent manner in VSMC. Arachidonyl trifluoromethyl ketone, a potent and specific inhibitor of cPLA(2), 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 cPLA(2,) arachidonic acid release, and DNA synthesis in VSMC. Together, these results suggest that induction of expression of cPLA(2) 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.
Yellaturu
Chandrahasa R
CR
Department of Physiology and the Center for Vascular Biology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Rao
Gadiparthi N
GN
D000818:Animals; D000077214:Becaplermin; D015153:Blotting, Western; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005799:Genes, Dominant; D017930:Genes, Reporter; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism* / Q000502:physiology*; D054467:Phospholipases A2; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D004268:DNA-Binding Proteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D000077214:Becaplermin; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases; C507906:Jak1 protein, rat; C507927:Jak2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D010741:Phospholipases A; D054467:Phospholipases A2