Phosphorylation of p42/44(MAPK) by various signal transduction pathways activates cytosolic phospholipase A(2) to variable degrees

J Biol Chem. 2001 Aug 3;276(31):28976-83. doi: 10.1074/jbc.M101361200. Epub 2001 Jun 4.


Arachidonic acid has been implicated to play a role in physiological and pathophysiological processes and is selectively released by the 85-kDa cytosolic phospholipase A(2) (cPLA(2)). The activity of cPLA(2) is regulated by calcium, translocating the enzyme to its substrate, and by phosphorylation by a mitogen-activated protein kinase (MAPK) family member and a MAPK-activated protein kinase. In this study, the signal transduction pathways in growth factor-induced phosphorylation of p42/44(MAPK) and cPLA(2) activation were investigated in Her14 fibroblasts. p42/44(MAPK) in response to epidermal growth factor was not only phosphorylated via the Raf-MEK pathway but mainly through protein kinase C (PKC) or a related or unrelated kinase in which the phosphorylated p42/44(MAPK) corresponded with cPLA(2) activity. Serum-induced phosphorylation of p42/44(MAPK) also corresponded with cPLA(2) activity but is predominantly mediated via Raf-MEK and partly through PKC or a related or unrelated kinase. In contrast, activation of PKC by phorbol ester did not result in increased cPLA(2) activity, while p42/44(MAPK) is phosphorylated, mainly via Raf-MEK and through MEK. Moreover, p42/44(MAPK) phosphorylation is present in quiescent and proliferating cells, and p42/44(MAPK) is entirely phosphorylated via Raf-MEK, but it only corresponds to cPLA(2) activity in the former cells. Collectively, these data show that p42/44(MAPK) in proliferating, quiescent, and stimulated cells is phosphorylated by various signal transduction pathways, suggesting the activation of different populations of p42/44(MAPK) and cPLA(2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Butadienes / pharmacology
  • Calcium / physiology
  • Cytosol / enzymology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology
  • Flavonoids / pharmacology
  • Humans
  • Kinetics
  • MAP Kinase Kinase Kinase 1*
  • MAP Kinase Signaling System / physiology
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nitriles / pharmacology
  • Phospholipases A / metabolism*
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction / physiology*
  • Transfection


  • Butadienes
  • Enzyme Inhibitors
  • Flavonoids
  • Nitriles
  • Recombinant Proteins
  • U 0126
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • Map3k1 protein, mouse
  • Phospholipases A
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Calcium