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Role of MSK1 in the signaling pathway leading to VEGF‐mediated PAF synthesis in endothelial cells
Author(s) -
Marchand Catherine,
Favier Judith,
Sirois Martin G.
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20840
Subject(s) - vascular endothelial growth factor , microbiology and biotechnology , mitogen activated protein kinase , kinase , p38 mitogen activated protein kinases , protein kinase a , transfection , vascular endothelial growth factor a , chemistry , biology , biochemistry , vegf receptors , cancer research , gene
Vascular endothelial growth factor (VEGF) inflammatory effects require acute platelet‐activating factor (PAF) synthesis by endothelial cells (EC). We previously reported that VEGF‐mediated PAF synthesis involves the activation of VEGF receptor‐2/Neuropilin‐1 complex, which is leading to the activation of p38 and p42/44 mitogen‐activated protein kinases (MAPKs) and group V secretory phospholipase A 2 (sPLA 2 ‐V). As the mechanisms regulating sPLA 2 ‐V remain unknown, we addressed the role of the mitogen‐ and stress‐activated protein kinase‐1 (MSK1), which can be rapidly and transiently activated by p38 or p42/44 MAPKs. In native bovine aortic endothelial cells (BAEC), we observed a constitutive protein interaction of MSK1 with p38, p42/44 MAPKs, and sPLA 2 ‐V. These protein interactions were maintained in BAEC transfected either with the empty vector pCDNA3.1, wild‐type MSK1 (MSK1‐WT) or N‐terminal dead kinase MSK1 mutant (MSK1‐D195A). However, in BAEC expressing C‐terminal dead kinase MSK1 mutant (MSK1‐D565A), the interaction between MSK1 and sPLA 2 ‐V was reduced by 82% and 90% under basal and VEGF‐treated conditions as compared to native BAEC. Treatment with VEGF for 15 min increased basal PAF synthesis in native BAEC, pCDNA3.1, MSK1‐WT, and MSK1‐D195A by 166%, 139%, 125%, and 82%, respectively. In contrast, PAF synthesis was prevented in cells expressing MSK1‐D565A mutant. These results demonstrate the essential role of the C‐terminal domain of MSK1 for its constitutive interaction with sPLA 2 ‐V, which appears essential to support VEGF‐mediated PAF synthesis. J. Cell. Biochem. 98: 1095–1105, 2006. © 2006 Wiley‐Liss, Inc.