RGD Reference Report - An essential role of the Jak-2/STAT-3/cytosolic phospholipase A(2) axis in platelet-derived growth factor BB-induced vascular smooth muscle cell motility. - Rat Genome Database

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

Authors: Neeli, I  Liu, Z  Dronadula, N  Ma, ZA  Rao, GN 
Citation: Neeli I, etal., J Biol Chem. 2004 Oct 29;279(44):46122-8. Epub 2004 Aug 22.
RGD ID: 1641932
Pubmed: PMID:15322111   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M406922200   (Journal Full-text)

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 A(2) (cPLA(2)). 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 cPLA(2) in a Jak-2/STAT-3-dependent manner, and pharmacological inhibitors of cPLA(2) prevented PDGFBB-induced VSMC motility. Furthermore, either exogenous addition of arachidonic acid or forced expression of cPLA(2) 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/cPLA(2) signaling axis.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Jak2Ratpositive regulation of DNA binding  IMP Stat3RGD 
Jak2Ratpositive regulation of DNA-binding transcription factor activity  IMP Stat3RGD 

Objects Annotated

Genes (Rattus norvegicus)
Jak2  (Janus kinase 2)


Additional Information