BetaPix-a enhances the activity of phospholipase Cgamma1 by binding SH3 domain in breast cancer.
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.
Bae
Ji-Yeon
JY
Cancer Research Institute, College of Medicine, Seoul National University, Yongon-dong, Chongno-gu, Seoul 110-744, South Korea.
Ahn
Soo-Jung
SJ
Lee
Jeong Eon
JE
Kim
Jung-Eun
JE
Han
Mi-Ryung
MR
Han
Wonshik
W
Kim
Seok Won
SW
Shin
Hyuk Jai
HJ
Lee
Seung Joon
SJ
Park
Dongeun
D
Noh
Dong-Young
DY
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000502:physiology*; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D007150:Immunohistochemistry; D051379:Mice; D041681:NIH 3T3 Cells; D051966:Phospholipase C gamma; D011485:Protein Binding; D064067:Rho Guanine Nucleotide Exchange Factors; D010738:Type C Phospholipases / Q000378:metabolism*; D018909:src Homology Domains
C576607:Arhgef7 protein, mouse; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D010738:Type C Phospholipases; D051966:Phospholipase C gamma