Correlations between the expression, phosphotyrosine content and enzymatic activity of focal adhesion kinase, pp125FAK, in tumor and nontransformed cells.
Focal adhesion kinase (pp125FAK, FAK) is a structurally unique nonreceptor tyrosine kinase that is localized in the focal adhesion plaques. Activation or modulation of this kinase has been associated with several signaling pathways including integrin mediated processes, mitogenic stimulation by neuropeptides and platelet-derived growth factor as well as oncogene-mediated transformation. These observations suggest that FAK may play a potential role in tumorigenesis and/or tumor invasiveness. Since the phosphotyrosine content of FAK has been implicated in both the activation of its catalytic activity and the recruitment of SH2 containing proteins, the expression, phosphorylation status and enzymatic activity of FAK was examined in a number of human tumor and normal cell lines. FAK was detectable in all cell lines with fairly consistent levels of expression. In contrast, constitutive tyrosine phosphorylation of FAK was quite variable among both normal and tumor cell lines. A direct correlation (correlation coefficient = 0.94) was observed between FAK activity and phosphotyrosine content. Within the cell lines examined, colon carcinomas exhibited marked elevation in FAK tyrosine kinase activity and phosphotyrosine content. These data suggest that colon carcinomas have elevated FAK activity in comparison to other tumor types and provide further support that the catalytic activity of FAK is enhanced by its phosphotyrosine content.
Withers
B E
BE
Department of Cancer Research, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Hanks
S K
SK
Fry
D W
DW
D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012016:Reference Values; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human