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J. Cell Biol.,
Volume 144, Number 2, January 25, 1999 315-324


* Department of Molecular Biology and Biochemistry, Rutgers University, Nelson Labs, Piscataway, New Jersey 08855; At mitosis, focal adhesions disassemble and
the signal transduction from focal adhesions is inactivated. We have found that components of focal adhesions including focal adhesion kinase (FAK), paxillin,
and p130CAS (CAS) are serine/threonine phosphorylated during mitosis when all three proteins are tyrosine
dephosphorylated. Mitosis-specific phosphorylation
continues past cytokinesis and is reversed during post-mitotic cell spreading.
We have found two significant alterations in FAK-mediated signal transduction during mitosis. First, the
association of FAK with CAS or c-Src is greatly inhibited, with levels decreasing to 16 and 13% of the interphase levels, respectively. Second, mitotic FAK shows
decreased binding to a peptide mimicking the cytoplasmic domain of beta-integrin when compared with FAK
of interphase cells. Mitosis-specific phosphorylation is
responsible for the disruption of FAK/CAS binding because dephosphorylation of mitotic FAK in vitro by
protein serine/threonine phosphatase 1 restores the
ability of FAK to associate with CAS, though not with
c-Src. These results suggest that mitosis-specific modification of FAK uncouples signal transduction pathways
involving integrin, CAS, and c-Src, and may maintain
FAK in an inactive state until post-mitotic spreading.
Department of Cancer Research, Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan 48105; § Department of
Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and
Cancer Institute of New Jersey, Busch
Campus, Piscataway, New Jersey 08855
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