LYSOPHOSPHATIDIC ACID INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATIONOF MAP-KINASE AND FOCAL ADHESION KINASE IN CULTURED SWISS 3T3 CELLS

Lysophosphatidic acid (LPA) added to serum-starved Swiss 3T3 cells ind uced, in a time- and concentration-dependent manner, tyrosine phosphor ylation 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 (M AP-kinase) and focal adhesion kinase (FAK), respectively. by immunopre cipitation and immunoblot analysis. Tyrosine phosphorylation of p64 pe aked 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 a ctivity of MAP-kinase determined as phosphorylation of myelin basic pr otein increased transiently about 3-fold at 5 min, and correlated with tyrosine phosphorylation. These results indicate that tyrosine phosph orylation of these proteins is a part of the signal transduction by LP A and may be involved in its mitogenic responses.