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

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 wer...

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Bibliographic Details
Published in:The EMBO journal 2000-02, Vol.19 (4), p.642-654
Main Authors: Qian, Xiaolan, Esteban, Luis, Vass, William C., Upadhyaya, Cheerag, Papageorge, Alex G., Yienger, Kate, Ward, Jerrold M., Lowy, Douglas R., Santos, Eugenio
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Cell Line, Transformed
DNA Primers - genetics
Epidermal Growth Factor - pharmacology
ErbB Receptors - genetics
ErbB Receptors - metabolism
ERK activation pathway
ERK protein
Female
Gene Expression
Genes, ras
Genes, src
genomic disruption
In Situ Hybridization
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases - metabolism
Molecular Sequence Data
Placenta - metabolism
placental development
Pregnancy
Ras protein
ras Proteins - genetics
ras Proteins - metabolism
Ras signaling
Signal Transduction
Son of Sevenless Proteins - genetics
Son of Sevenless Proteins - metabolism
sos1 gene
Sos1 protein
SOS1 Protein - genetics
SOS1 Protein - metabolism
Sos2 protein
spongiotrophoblasts
v-Src gene
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1093/emboj/19.4.642