CORRELATIONS BETWEEN THE EXPRESSION, PHOSPHOTYROSINE CONTENT AND ENZYMATIC-ACTIVITY OF FOCAL ADHESION KINASE, PP125(FAK), IN TUMOR AND NONTRANSFORMED CELLS

Focal adhesion kinase (pp125(FAK), FAK) is a structurally unique nonre ceptor tyrosine kinase that is localized in the focal adhesion plaques . Activation or modulation of this kinase has been associated with sev eral signaling pathways including integrin mediated processes, mitogen ic stimulation by neuropeptides and platelet-derived growth factor as well as oncogene-mediated transformation. These observations suggest t hat FAK may play a potential role in tumorigenesis and/or tumor invasi veness. Since the phosphotyrosine content of FAK has been implicated i n both the activation of its catalytic activity and the recruitment of SH2 containing proteins, the expression, phosphorylation status and e nzymatic activity of FAK was examined in a number of human tumor and n ormal cell lines. FAK was detectable in all cell lines with fairly con sistent levels of expression. In contrast, constitutive tyrosine phosp horylation of FAK was quite variable among both normal and tumor cell lines. A direct correlation (correlation coefficient = 0.94) was obser ved between FAK activity and phosphotyrosine content. Within the cell lines examined, colon carcinomas exhibited marked elevation in FAK tyr osine kinase activity and phosphotyrosine content. These data suggest that colon carcinomas have elevated FAK activity in comparison to othe r tumor types and provide further support that the catalytic activity of FAK is enhanced by its phosphotyrosine content.