A second protein-tyrosine kinase (PTK) of the focal adhesion kinase (FAK) subfamily, cell adhesion kinase (CAK), was identified by cDNA cloning. The rat CAK is a 115.7-kDa PTK that contains N- and C-terminal domains of 418 and 330 amino acid residues besides the central kinase domain. The rat CAK has a homology with mouse FAK over their entire lengths except for the extreme N-terminal 88 residues and shares 45% overall sequence identity (60% identical in the catalytic domain), which indicates that CAK is a protein structurally related to but different from FAK. The CAK gene is less evenly expressed in a variety of rat organs than the FAK gene. Anti-CAK antibody immunoprecipitated a 113-kDa protein from rat brain, 3Y1 fibroblasts, and COS-7 cells transfected with CAK cDNA. The tyrosine-phosphorylated state of CAK was not reduced on trypsinization, nor enhanced in response to plating 3Y1 cells onto fibronectin. CAK localized to sites of cell-to-cell contact in COS-7 transfected with CAK cDNA, in which FAK was found at the bottom of the cells. Thus, CAK is a PTK possibly participating in the signal transduction regulated by cell-to-cell contacts.

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