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  • The EMBO Journal (2000) 19, 642 - 654
  • doi:10.1093/emboj/19.4.642

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

Xiaolan Qian1, Luis Esteban2, William C. Vass1, Cheerag Upadhyaya1, Alex G. Papageorge1, Kate Yienger2, Jerrold M. Ward3, Douglas R. Lowy1 and Eugenio Santos2,4

  1. Laboratory of Cellular Oncology Bethesda, National Cancer Institute, Bethesda, MD 20892 USA
  2. Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892 USA
  3. Veterinary and Tumor Pathology Section, National Cancer Institute, Frederick, MD 21702, USA
  4. Present address: Centro de Investigatión del cáncer, CSIC-USAL, Campus Unamuno, Universidad Salamanca, 37007 Salamanca, Spain.

Correspondence to:

Douglas R. Lowy, E-mail: drl@helix.nih.gov

Received 25 October 1999; Accepted 7 December 1999; Revised 7 December 1999

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 RasdotGTP and ERK responses when treated with EGF for less than or equal to10 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 greater than or equal to90 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.

  • Keywords:

    • ERK activation pathway,
    • genomic disruption,
    • placental development,
    • Ras signaling,
    • spongiotrophoblasts