Dissociation of FAK/p130(CAS)/c-Src complex during mitosis: Role of mitosis-specific serine phosphorylation of FAK

At mitosis, focal adhesions disassemble and the signal transduction from fo cal adhesions is inactivated. We have found that components of focal adhesi ons including focal adhesion kinase (FAK), paxillin, and p130(CAS) (CAS) ar e serine/threonine phosphorylated during mitosis when all three proteins ar e tyrosine dephosphorylated. Mitosis-specific phosphorylation continues pas t cytokinesis and is reversed during postmitotic cell spreading. We have found two significant alterations in FAK-mediated signal transducti on during mitosis. First, the association of FAK with CAS or c-Src is great ly inhibited, with levels decreasing to 16 and 13% of the interphase levels , respectively, Second, mitotic FAK shows decreased binding to a peptide mi micking the cytoplasmic domain of beta-integrin when compared with FAK of i nterphase cells. Mitosis-specific phosphorylation is responsible for the di sruption of FAK/CAS binding because dephosphorylation of mitotic FAK in vit ro by protein serine/threonine phosphatase 1 restores the ability of FAK to associate with GAS, though not with c-Src, These results suggest that mito sis-specific modification of FAK uncouples signal transduction pathways inv olving integrin, GAS, and c-Src, and may maintain FAK in an inactive state until post-mitotic spreading.