Interactions That Contribute to Fak Activation

DANIELLE MARIE SCHESWOHL INTERACTIONS THAT CONTRIBUTE TO FAK ACTIVATION (Under the direction of Michael D Schaller) Focal adhesion kinase (FAK) is an important regulatory protein that integrates signals from integrins and growth factor receptors to control cell growth, survival, and migration. FAK function is tightly regulated and the complete mechanism of activation remains to be resolved. The FAT domain of FAK associates with the scaffolding protein paxillin as a major mechanism of FAK localization. Structural insights have been used to design point mutations to disrupt FAK binding to paxillin and resulting defects in FAK function have been characterized. The FERM domain of FAK is tho ught to play an important role in relaying biological signals. This domain is involved in an intramolecular interaction with the FAK catalytic domain that severely inhibits activity. I hypothesize that FERM domain associations disrupt the inhibitory association between the FERM and catalytic domains, thus activating FAK. A mutagenesis strategy has been used to identify binding sites on the FERM domain.