MAP3K11 is required for serum-stimulated cell proliferation and for mitogen and cytokine activation of p38, ERK, and JNK1. MAP3K11 also plays a role in mitogenstimulated phosphorylation and activation of BRAF, without phosphorylating BRAF directly. Thus, MAP3K11 functions as a node in the mitogen and stress signaling pathways. We have previously shown that activation of the MAP kinase pathway correlates with prostate cancer progression in a variety of settings and determined that stress kinase signaling regulates AR Ser 650 phosphorylation. In this study, we confirmed that stress kinase signaling regulates AR Ser 650 phosphorylation; knockdown of MAP3K11 stoichiometrically decreased PMA-induced AR Ser 650 phosphorylation. Modulation of Ser 650 phosphorylation may be regulating AR transcriptional activity of the AR target genes that were altered upon MAP3K11 knockdown, including TMPRSS2, SGK, ORM1, DKK and FST. We also found that the castration-resistant prostate cancer AR regulated M-phase genes CDC20, CDK1, and UBE2C, were decreased in response to MAP3K11 knockdown, although the decrease in transcription of these genes may reflect the inhibition of growth triggered by MAP3K11 knockdown and not represent altered AR transcriptional activity. Our screen also identified other stress kinases, including MAP3K7, MAP4K3, and MAPKAPK5, which underscores the critical nature of stress kinase signaling in regulating prostate cancer cell growth. DGK catalyzes the phosphorylation of DAG by converting it to PA, thereby exchanging one second messenger for Epoxomicin another and activating protein kinase C. There is increasing evidence suggesting that DGKD is involved in regulating DAG and PA levels in response to various growth factors and hormones. DGKD was reported to interact with RACK1, a protein that we had previously demonstrated as an AR interacting protein that regulates AR phosphorylation and transcriptional activity. Thus, DGKD may contribute to AR regulation through RACK1. However, knockdown of DGKD did not have a significant effect on AR transcriptional activity. Previous research has shown that in the absence of DGKD, EGFR signaling is decreased because both expression and kinase activity are inhibited. This effect on EGFR is a result of a decrease in a deubiquitinase, USP-8, and therefore increased ubiquitination and degradation of the EGFR. Growth factor signaling is a known regulator of prostate cancer cell growth. It is therefore possible that the growth effect that corresponds with DGKD knockdown is the result of altered receptor tyrosine kinase signaling. ICK is a serine/threonine kinase containing a dual phosphorylation site found in mitogen-activating protein kinases whose activity is regulated by cell cycle-related kinase and human protein phosphatase 5. ICK is related to male germ cell-associated protein kinase. MAK is an AR coregulator that directly binds the AR in co-immunoprecipitation experiments and enhances AR-dependent transcription in a kinasedependent manner. Inhibition of MAK with either RNAi or a kinase-dead form decreased LNCaP cell growth.