Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-γ1

Myung Jong Kim, Jong Soo Chang, Seung Kook Park, Jong Ik Hwang, Sung Ho Ryu, Pann Ghill Suh*

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

A recent report that microinjection of the SH3 domain of PLC-γ1 could induce DNA synthesis raised the functional importance of the SH3 domain of PLC-γ1 in mitogenic signaling. In this report, we provide evidence that SOS1, a p21Ras-specific guanine nucleotide exchange factor, directly binds to the SH3 domain of PLC-γ1, and that the SH3 domain of PLC-γ1 is involved in SOS1-mediated p21Ras activation. SOS 1 was coprecipitated with the GST-fused SH3 domain of PLC-γ1 in vitro. The interaction between SOS1 and the PLC-γ1 SH3 domain is mediated by direct physical interaction. The carboxyl-terminal proline-rich domain of SOS1 is involved in the interaction with the PLC-γ1 SH3 domain. Moreover, PLC-γ1 could be co-immunoprecipitated with SOS1 antibody in cell lysates. From transient expression studies, we could demonstrate that the SH3 domain of PLC-γ1 is necessary for the association with SOS1 in vivo. Intriguingly, overexpression of the SH3 domain of PLC-γ1, lipase-inactive PLC-γ1, or wild-type PLC-γ1 elevated p21Ras activity and ERK activity when compared with vector transfected cells. The PLC-γ1 mutant lacking the SH3 domain could not activate p21Ras, p21Ras activities in cell lines overexpressing either PLC-γ1 or the SH2-SH2-SH3 domain of PLC-γ1 were elevated about 2-fold compared to vector transfected cells. This study is the first to demonstrate that the PLC-γ1 SH3 domain enhances p21Ras activity, and that the SH3 domain of PLC-γ1 may be involved in the SOS1-mediated signaling pathway.

Original languageEnglish (US)
Pages (from-to)8674-8682
Number of pages9
JournalBiochemistry
Volume39
Issue number29
DOIs
StatePublished - Jul 25 2000

ASJC Scopus subject areas

  • Biochemistry

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    Kim, M. J., Chang, J. S., Park, S. K., Hwang, J. I., Ryu, S. H., & Suh, P. G. (2000). Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-γ1. Biochemistry, 39(29), 8674-8682. https://doi.org/10.1021/bi992558t