BetaPix-a enhances the activity of phospholipase Cgamma1 by binding SH3 domain in breast cancer.

Abstract:

:Phospholipase C-gamma1 (PLCgamma1) 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 PLCgamma1 in PLCgamma1-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 PLCgamma1 as the guanine nucleotide exchange factor, p21-activated protein kinase-interacting exchange factor-a (betaPix-a). BetaPix-a co-immunoprecipitated with PLCgamma1 in breast cancer tissues extracts and in MCF7 and MDA-MB-231 cell extracts. In addition, PDGF-stimulated PLCgamma1 activity was elevated in betaPix-a-overexpressing NIH3T3 cells. Our results suggest that betaPix-a binds to the Src homology domain 3 of PLCgamma1 and promotes tumor growth in breast cancer by enhancing the activity PLCgamma1.

journal_name

J Cell Biochem

authors

Bae JY,Ahn SJ,Lee JE,Kim JE,Han MR,Han W,Kim SW,Shin HJ,Lee SJ,Park D,Noh DY

doi

10.1002/jcb.20357

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

1010-6

issue

5

eissn

0730-2312

issn

1097-4644

journal_volume

94

pub_type

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