INVESTIGADORES
MUNARRIZ Eliana Rosa
artículos
Título:
Polyomavirus large T antigen induces alterations in cytoplasmic signalling pathways involving Shc activation.
Autor/es:
GOTTIFREDI V, PELICCI G, MUNARRIZ E, MAIONE R, PELICCI PG, AMATI P.
Revista:
JOURNAL OF VIROLOGY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Año: 1999 p. 1427 - 1437
ISSN:
0022-538X
Resumen:
It has been extensively demonstrated that growth factors play a key role
in the regulation of proliferation. Several lines of evidence support
the hypothesis that for the induction of cell cycle progression in the
absence of exogenous growth factors, oncogenes must either induce
autocrine growth factor secretion or, alternatively, activate their
receptors or their receptor substrates. Cells expressing polyomavirus
large T antigen (PyLT) display reduced growth factor requirements, but
the mechanisms underlying this phenomenon have yet to be explored. We
conducted tests to see whether the reduction in growth factor
requirements induced by PyLT was related to alterations of growth
factor-dependent signals. To this end, we analyzed the phosphorylation
status of a universal tyrosine kinase substrate, the transforming Shc
adapter protein, in fibroblasts expressing the viral oncogene. We report
that the level of Shc phosphorylation does not decrease in
PyLT-expressing fibroblasts after growth factor withdrawal and that this
PyLT-mediated effect does not require interaction with protein encoded
by the retinoblastoma susceptibility gene. We also found that the
chronic activation of the adapter protein is correlated with the binding
of Shc to Grb-2 and with defects in the downregulation of
mitogen-activated protein kinases. In fibroblasts expressing the nuclear
oncoprotein, we also observed the formation of a PyLT-Shc complex that
might be involved in constitutive phosphorylation of the adapter
protein. Viewed comprehensively, these results suggest that the cell
cycle progression induced by PyLT may depend not only on the direct
inactivation of nuclear antioncogene products but also on the indirect
induction, through the alteration of cytoplasmic pathways, of growth
factor-dependent nuclear signals.