The N Termini of Focal Adhesion Kinase Family Members Regulate Substrate Phosphorylation, Localization, and Cell Morphology

• Published in: The Journal of biological chemistry 2002-11, Vol.277 (47), p.45644-45654
• Main Authors: Dunty, Jill M, Schaller, Michael D
• Format: Article
• Language: English
• Subjects: Animals; Cell Cycle - physiology; Cell Size; Chick Embryo; CSK Tyrosine-Protein Kinase; Enzyme Activation; Focal Adhesion Kinase 2; Focal Adhesion Protein-Tyrosine Kinases; Immunohistochemistry; Multigene Family; Mutation; Phosphorylation; Protein Structure, Tertiary; Protein-Tyrosine Kinases - chemistry; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Signal Transduction - physiology; src-Family Kinases; Tyrosine - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M201779200

The focal adhesion kinase (FAK) and cell adhesion kinase β (CAKβ, PYK2, CADTK, RAFTK) are highly homologous FAK family members, yet clearly have unique roles in the cell. Comparative analyses of FAK and CAKβ have revealed intriguing differences in their activities. These differences were investigated further through the characterization of a set of FAK/CAKβ chimeric kinases. CAKβ exhibited greater catalytic activity than FAK in vitro , providing a molecular basis for differential substrate phosphorylation by FAK and CAKβ in vivo . Furthermore, the N terminus may regulate catalytic activity since chimeras containing the FAK N terminus and CAKβ catalytic domain exhibited a striking high level of catalytic activity and substrate phosphorylation. Unexpectedly, a modulatory role for the N termini in subcellular localization was also revealed. Chimeras containing the FAK N terminus and CAKβ C terminus localized to focal adhesions, whereas chimeras containing the N and C termini of CAKβ did not. Finally, prominent changes in cell morphology were induced upon expression of chimeras containing the CAKβ N terminus, which were not associated with apoptotic cell death, cell cycle progression delay, or changes in Rho activity. These results demonstrate novel regulatory roles for the N terminus of FAK family kinases.