INVESTIGADORES
GONZALEZ SANCHEZ WUSENER Ana Elena
congresos y reuniones científicas
Título:
SRC ACTIVATION IN NASCENT ADHESIONS DEPENDS ON INTEGRINS, PTP1B AND PAXILLIN DEPHOSPHORYLATION
Autor/es:
GONZÁLEZ S. WUSENER AE; BURDISSO J.; AND ARREGUI CO.
Lugar:
Puerto Madryn, Chubut
Reunión:
Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
PTP1B is an ER-bound tyrosine phosphatase implicated in the maturation and dynamics of cell-matrix adhesions through Src-dependent pathways. Here, we examined the mechanisms underlying the localization of active Src in nascent cell-matrix adhesions. Immunofluorescence analysis of total Src showed a uniform punctate distribution in both PTP1B WT (WT) and PTP1B KO (KO) cells shortly plated on fibronectin. However, active Src accumulated in a peripheral ring of nascent adhesions only in WT cells. This distribution was lost when cells were plated on poly-L-lysine. Adhesion of WT cells to vitronectin, which specifically depends on beta3 integrin, showed accumulation of active Src in nascent adhesions. Conversely, inhibition of beta3 integrin on cells plated on fibronectin, which also adhere through beta1 integrin, abolished this distribution. Paxillin localization in nascent adhesions did not depend on Src expression, as revealed by analysis of SYF cells. However, active Src localization depended on paxillin, since null cells were unable to show its accumulation at the peripheral ring. Reconstitution with the double paxillin mutant Y31F/Y118F and with the single mutant Y118F, but not Y31F, rescued active Src localization to nascent adhesions. Thus, dephosphorylation of paxillin, likely by PTP1B, promotes Src activity at beta3 integrin-dependent nascent adhesion sites. Supported by ANPCyT.