Open AccessSH2D4A regulates cell proliferation via the ERα/PLC-γ/PKC pathway
Author(s) -
Tingting Li,
Wei Li,
Jingyu Lu,
Hong Lv,
Yinghui Li,
Yanyan Zhao
Publication year - 2009
Publication title -
bmb reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.511
H-Index - 77
eISSN - 1976-670X
pISSN - 1976-6696
DOI - 10.5483/bmbrep.2009.42.8.516
Subject(s) - microbiology and biotechnology , protein kinase c , cell growth , chemistry , signal transduction , cell , biology , biochemistry
SH2D4A, comprising a single SH2 domain, is a novel protein of the SH2 signaling protein family. We have previously demonstrated SH2D4A is expressed ubiquitously in various tissues and is located in the cytoplasm. In this study we investigated the function of SH2D4A in human embryonic kidney (HEK) 293 cells using interaction analysis, cell proliferation assays, and kinase activity detection. SH2D4A was found to directly bind to estrogen receptor alpha (ERalpha), and prevent the recruitment of phospholipase C-gamma (PLC-gamma) to ERalpha. Moreover, we observed its inhibitory effects on estrogen-induced cell proliferation, involving the protein kinase C (PKC) signaling pathway. Together, these findings suggested that SH2D4A inhibited cell proliferation by suppression of the ERalpha/PLC-gamma/PKC signaling pathway. SH2D4A may be useful for the development of a new anti-cancer drug acting as an ER signaling modulator.