Direct interaction of SOS1 ras exchange protein with the SH3 domain of phospholipase C-gamma 1
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SCOPUS
- Title
- Direct interaction of SOS1 ras exchange protein with the SH3 domain of phospholipase C-gamma 1
- Authors
- Kim, MJ; Chang, JS; Park, SK; Hwang, JI; Ryu, SH; Suh, PG
- Date Issued
- 2000-07-25
- Publisher
- AMER CHEMICAL SOC
- Abstract
- A recent report that microinjection of the SH3 domain of PLC-gamma 1 could induce DNA synthesis raised the functional importance of the SH3 domain of PLC-gamma 1 in mitogenic signaling. In this report, we provide evidence that SOS1, a p2Ras-specific guanine nucleotide exchange factor, directly binds to the SH3 domain of PLC-gamma 1, and that the SH3 domain of 1 is involved in SOS1-mediated p21Ras activation. SOS1 was coprecipitated with the GST-fused SH3 domain of PLC-gamma 1 in vitro. The interaction between SOS1 and the PLC-gamma 1 SH3 domain is mediated by direct physical interaction. The carboxyl-terminal proline-rich domain of SOS1 is involved in the interaction with the PLC-gamma 1 SH3 domain. Moreover, PLC-gamma 1 could be co-immunoprecipitated with SOS1 antibody in cell lysates. From transient expression studies, we could demonstrate that the SH3 domain of PLC-gamma 1 is necessary for the association with SOS1 in vivo. Intriguingly, overexpression of the SH3 domain of PLC-gamma 1, lipase-inactive PLC-gamma 1, or wild-type PLC-gamma 1 elevated p21Ras activity and ERK activity when compared with vector transfected cells. The PLC-gamma 1 mutant lacking the SH3 domain could not activate p21Ras. p21Ras activities in cell lines overexpressing either PLC-gamma 1 or the SH2-SH2-SH3 domain of PLC-gamma 1 were elevated about 2-fold compared to vector transfected cells. This study is the first to demonstrate that the PLC-gamma 1 SH3 domain enhances p21Ras activity, and that the SH3 domain of PLC-gamma 1 may be involved in the SOS1-mediated signaling pathway.
- Keywords
- TYROSINE KINASE; GROWTH-FACTOR; INOSITOL TRISPHOSPHATE; SIGNAL TRANSDUCTION; ELEVATED CONTENT; DNA-SYNTHESIS; FACTOR HSOS1; C ISOZYMES; GRB2; RECEPTOR
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/19915
- DOI
- 10.1021/bi992558t
- ISSN
- 0006-2960
- Article Type
- Article
- Citation
- BIOCHEMISTRY, vol. 39, no. 29, page. 8674 - 8682, 2000-07-25
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- There are no files associated with this item.
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