Regulation of cell-matrix adhesion and cell migration by PTP1B

BURDISSO JE; AGUIRRE CE; MANSILLA SF; HERNANDEZ MV; ARREGUI CO

Mar del Plata

Congreso; XLIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular

Our previous work shows that ER-bound PTP1B associates with integrin complexes, and that is required for cell-matrix adhesion and spreading. Further, we and others showed that the protein tyrosine kinase Src is a substrate of PTP1B. In this work we examined the role of Src family members in the localization of PTP1B to cell-matrix adhesion sites, and the role of PTP1B in the turnover of the adhesive sites, and in cell migration. Using cell lines deficient in different members of the Src family, we found that Fyn but not Src plays an essential role in the localization of PTP1B to the cell-matrix adhesion sites. In addition, PTP1B and Fyn colocalize in small foci at the leading edge and at patches of the ventral membrane which also contain F-actin. In PTP1B knockout cells (KO cells), small focal complexes at the protruding lamella are more dynamic and incorporate less -actinin than in cells reconstituted with wild type PTP1B (WT cells). KO cells display frequent changes in speed and pause periods, frequent changes in the direction of migration, and long and persistent trailing tails compared to theWTcells. Our results reveal a tight functional link between PTP1B and Fyn at cell-matrix adhesion sites. In addition, our data suggest a function of PTP1B in cell migration and cellmatrix turnover, which at least partly may involve the regulation of rho GTPases.