βPix-a enhances the activity of phospholipase Cγ1 by binding SH3 domain in breast cancer
✍ Scribed by Ji-Yeon Bae; Soo-Jung Ahn; Jeong Eon Lee; Jung-Eun Kim; Mi-Ryung Han; Wonshik Han; Seok Won Kim; Hyuk Jai Shin; Seung Joon Lee; Dongeun Park; Dong-Young Noh
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 168 KB
- Volume
- 94
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Phospholipase C‐γ1 (PLCγ1) plays a critical role in cell growth and proliferation by generating the second messengers, diacylglycerol and 1, 4, 5‐inositol triphosphate. To investigate the roles of Src homology domain 2 and domain 3 of PLCγ1 in PLCγ1‐mediated cell signaling, we characterized some proteins binding to these domains in the MCF7 and MDA‐MB‐231 breast cancer cell lines. Of the several proteins that bind to glutathione‐S‐transferase‐SH2/SH2/SH3, we identified an 85 kDa protein that binds to the SH3 domain of PLCγ1 as the guanine nucleotide exchange factor, p21‐activated protein kinase‐interacting exchange factor‐a (βPix‐a). βPix‐a co‐immunoprecipitated with PLCγ1 in breast cancer tissues extracts and in MCF7 and MDA‐MB‐231 cell extracts. In addition, PDGF‐stimulated PLCγ1 activity was elevated in βPix‐a‐overexpressing NIH3T3 cells. Our results suggest that βPix‐a binds to the Src homology domain 3 of PLCγ1 and promotes tumor growth in breast cancer by enhancing the activity PLCγ1. J. Cell. Biochem. 94: 1010–1016, 2005. © 2004 Wiley‐Liss, Inc.