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

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.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-11-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M201779200PMID 12223467
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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