Lysophosphatidic acid induces tyrosine phosphorylation and activation of MAP-kinase and focal adhesion kinase in cultured Swiss 3T3 cells.
Lysophosphatidic acid (LPA) added to serum-starved Swiss 3T3 cells induced, in a time- and concentration-dependent manner, tyrosine phosphorylation of multiple proteins, including proteins of 43, 64, 88 kDa and a group of proteins between 110 and 130 kDa. Among them, two proteins, p43 and p120, were identified as mitogen-activated protein kinase (MAP-kinase) and focal adhesion kinase (FAK), respectively, by immunoprecipitation and immunoblot analysis. Tyrosine phosphorylation of p64 peaked at 1 min and declined rapidly, whereas that of MAP-kinase and FAK peaked at 5 and 10 min after the addition of LPA, respectively. The activity of MAP-kinase determined as phosphorylation of myelin basic protein increased transiently about 3-fold at 5 min, and correlated with tyrosine phosphorylation. These results indicate that tyrosine phosphorylation of these proteins is a part of the signal transduction by LPA and may be involved in its mitogenic responses.
Kumagai
N
N
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Morii
N
N
Fujisawa
K
K
Yoshimasa
T
T
Nakao
K
K
Narumiya
S
S
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D008246:Lysophospholipids; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1