c-Jun N-terminal kinase is necessary for platelet-derived growth factor-mediated chemotaxis in primary fibroblasts.
c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family. It has become clear that JNK does not only have a role in induction of stress responses but also in processes such as cell movement. In this report we demonstrate that JNK activity is necessary for platelet-derived growth factor (PDGF)-BB-induced chemotaxis of primary foreskin fibroblasts and in other cell types. PDGF-BB stimulation was found to lead to activation of JNK with a maximum after 30 min. Inhibition of JNK reduced Ser178 phosphorylation of the focal adhesion component paxillin. Paxillin phosphorylation at this site has been shown to be involved in the dynamics of focal adhesions and consequently cell migration. Moreover, we observed localization of JNK to the actin-dense membrane ruffles induced by PDGF-BB stimulation both using immunofluorescence staining and green fluorescent protein-tagged JNK. This suggests a role for JNK at the leading edge of the cell compatible with a function in cell migration. Furthermore, we show that phosphatidylinositol 3-kinase (PI 3-kinase), which has an established role in PDGF-stimulated cell migration, is necessary for PDGF-induced activation of JNK. In conclusion, JNK is a critical component downstream of PI 3-kinase that may be involved in PDGF-stimulated chemotaxis presumably by modulating the integrity of focal adhesions by phosphorylating its components.
Amagasaki
Kenichi
K
Ludwig Institute for Cancer Research, Uppsala University, Box 595, Biomedical Center, SE-751 24 Uppsala, Sweden.
Kaneto
Hideaki
H
Osaka University Graduate School of Medicine, Department of Internal Medicine and Therapeutics (A8), 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Heldin
Carl-Henrik
CH
Ludwig Institute for Cancer Research, Uppsala University, Box 595, Biomedical Center, SE-751 24 Uppsala, Sweden.
Lennartsson
Johan
J
Ludwig Institute for Cancer Research, Uppsala University, Box 595, Biomedical Center, SE-751 24 Uppsala, Sweden. Electronic address: Johan.Lennartsson@LICR.uu.se.
D002478:Cells, Cultured; D002633:Chemotaxis; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D051419:Paxillin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D012867:Skin / Q000166:cytology
D051419:Paxillin; D010982:Platelet-Derived Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases