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Cytokine‐mediated cPLA 2 phosphorylation is regulated by multiple MAPK family members
Author(s) -
Geijsen Niels,
Dijkers Pascale F,
Lammers Jan-Willem J,
Koenderman Leo,
Coffer Paul J
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01373-9
Subject(s) - phosphorylation , mapk/erk pathway , microbiology and biotechnology , kinase , p38 mitogen activated protein kinases , tyrosine phosphorylation , phosphorylation cascade , biology , mitogen activated protein kinase , protein kinase a , chemistry , protein phosphorylation
Cytosolic phospholipase A 2 (cPLA 2 ) plays a critical role in various neutrophil functions including the generation of leukotrienes and platelet‐activating factor release. Enzyme activity is regulated both by translocation to the membrane in a Ca 2+ ‐dependent manner and serine phosphorylation by members of the mitogen‐activated protein kinase (MAPK) family. In this report, we have investigated the role of granulocyte/macrophage colony‐stimulating factor (GM‐CSF)‐mediated signalling pathways in the regulation of cPLA 2 . GM‐CSF‐induced cPLA 2 phosphorylation was not affected by pharmacological inhibition of p38 MAPK, phosphatidylinositol 3‐kinase or Src. However, inhibition of extracellular signal‐regulated kinase (ERK) MAPK activation resulted in a partial inhibition of cPLA 2 phosphorylation, revealed in a slower onset of phosphorylation. A cell line stably transfected with the GM‐CSF receptor was used to further analyze GM‐CSF‐mediated cPLA 2 phosphorylation. Mutation of tyrosine residues 577 and 612 resulted in a delayed cPLA 2 phosphorylation similar to the pharmacological ERK inhibition. Furthermore, inhibition of p38 MAPK in cells bearing the double mutant βc577/612 completely abrogated GM‐CSF‐induced cPLA 2 phosphorylation. We conclude that GM‐CSF can mediate cPLA 2 phosphorylation through the redundant activation of both p38 and ERK MAP kinases.