The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties

AUTOR(ES)

Qian, Xiaolan

FONTE

Oxford University Press

RESUMO

Targeted disruption of both alleles of mouse sos1, which encodes a Ras-specific exchange factor, conferred mid-gestational embryonic lethality that was secondary to impaired placental development and was associated with very low placental ERK activity. The trophoblastic layers of sos1–/– embryos were poorly developed, correlating with high sos1 expression in wild-type trophoblasts. A sos1–/– cell line, which expressed readily detectable levels of the closely related Sos2 protein, formed complexes between Sos2, epidermal growth factor receptor (EGFR) and Shc efficiently, gave normal Ras⋅GTP and ERK responses when treated with EGF for ⩽10 min and was transformed readily by activated Ras. However, the sos1–/– cells were resistant to transformation by v–Src or by overexpressed EGFR and continuous EGF treatment, unlike sos1+/– or wild-type cells. This correlated with Sos2 binding less efficiently than Sos1 to EGFR and Shc in cells treated with EGF for ≥90 min or to v–Src and Shc in v–Src-expressing cells, and with less ERK activity. We conclude that Sos1 participates in both short- and long-term signaling, while Sos2-dependent signals are predominantly short-term.

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