Receptor for activated C kinase 1 (RACK1) and Src regulate the tyrosine phosphorylation and function of the androgen receptor.
The androgen receptor (AR) remains functionally important in the development and progression of prostate cancer even when the disease seems androgen "independent." Because signal transduction by growth factor receptors increases in advanced prostate cancer and is capable of sensitizing the AR to androgen, there is considerable interest in determining the mechanisms by which signaling systems can modulate AR function. We show herein that the adaptor/scaffolding protein receptor for activated C kinase 1 (RACK1), which was previously reported to interact with the AR, modulates the tyrosine phosphorylation of AR and its interaction with the Src tyrosine kinase. We also show that down-regulation of RACK1 by short interfering RNA inhibits growth and stimulates prostate-specific antigen transcription in androgen-treated prostate cancer cells. Our results suggest that RACK1 mediates the cross-talk of AR with additional binding partners, such as Src, and facilitates the tyrosine phosphorylation and transcriptional activity of the AR.
Kraus
Sarah
S
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, Virginia, USA.
Gioeli
Daniel
D
Vomastek
Tomas
T
Gordon
Vicki
V
Weber
Michael J
MJ
D000728:Androgens / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018450:Disease Progression; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000378:metabolism*
D000728:Androgens; D000075370:Receptors for Activated C Kinase; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; D019061:src-Family Kinases