ALTERNATIVELY SPLICED FOCAL ADHESION KINASE IN RAT-BRAIN WITH INCREASED AUTOPHOSPHORYLATION ACTIVITY

pp125 focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase trans ducing signals initiated by integrin engagement and G protein-coupled receptors, is highly expressed in brain. FAR from brain had a higher m olecular weight and an increased autophosphorylation activity, than fr om other tissues, In addition to a 9-base insertion in the 3'-coding r egion, which defines FAK(+), rat striatal FAK mRNAs contained several additional short exons, coding for peptides of 28, 6, and 7 residues, respectively (termed boxes 28, 6, and 7), surrounding the autophosphor ylated Tyr-397. In transfected COS 7 cells, the presence of boxes 6 an d 7 conferred an increased overall tyrosine phosphorylation, a higher phosphorylation of Tyr-397 assessed with a phosphorylation state-speci fic antibody, and a more active autophosphorylation in immune precipit ates. The presence of box 28 did not alter further these parameters, T wo-dimensional phosphopeptide maps of hippocampal FAK were identical t o those of FAR+6,7. The presence of the various exons did not alter th e interaction of FAK with c-Src, n-Src; or Fyn. Thus, several splice i soforms of FAK are preferentially expressed in rat brain, some of whic h have an increased autophosphorylation activity, suggesting that FAR may have specific properties in neurons.