SH2D4A regulates cell proliferation via the ERalpha/PLC-gamma/PKC pathway.
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.
Li
Tingting
T
Department of Medical Genetics, China Medical University, Shenyang 110001, China.
Li
Wei
W
Lu
Jingyu
J
Liu
Hong
H
Li
Yinghui
Y
Zhao
Yanyan
Y
D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051966:Phospholipase C gamma / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C474507:SH2D4A protein, human; D011493:Protein Kinase C; D051966:Phospholipase C gamma; D002118:Calcium