| http://purl.uniprot.org/citations/17494760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17494760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17494760 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of the androgen receptor (AR) may play a role in androgen-independent progression of prostate cancer. Multiple mechanisms of AR activation, including stimulation by tyrosine kinases, have been postulated. We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in advanced human prostate cancer. Here we provide the molecular basis for interplay between Ack1 and AR in prostate cancer cells. Activated Ack1 promoted androgen-independent growth of LNCaP and LAPC-4 prostate xenograft tumors, AR recruitment to the androgen-responsive enhancer, and androgen-inducible gene expression in the absence of androgen. Heregulin-stimulated HER2 activation induced Ack1 activation and AR tyrosine phosphorylation. Ack1 knockdown inhibited heregulin-dependent AR tyrosine phosphorylation, AR reporter activity, androgen-stimulated gene expression, and AR recruitment. Ack1 was recruited to the androgen-responsive enhancers after androgen and heregulin stimulation. In 8 of 18 primary androgen-independent prostate tumor samples, tyrosine-phosphorylated AR protein was detected and correlated with the detection of tyrosine-phosphorylated Ack1. Neither was elevated in androgen-dependent tumors or benign prostate samples. Activated Ack1 phosphorylated AR protein at Tyr-267 and Tyr-363, both located within the transactivation domain. Mutation of Tyr-267 completely abrogated and mutation of Tyr-363 reduced Ack1-induced AR reporter activation and recruitment of AR to the androgen-responsive enhancer. Expression of AR point mutants inhibited Ack1-driven xenograft tumor growth. Thus, Ack1 activated by surface signals or oncogenic mechanisms may directly enhance AR transcriptional function and promote androgen-independent progression of prostate cancer. Targeting the Ack1 kinase may be a potential therapeutic strategy in prostate cancer."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0700420104"xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0700420104"xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Earp H.S."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Earp H.S."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Mahajan N.P."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Mahajan N.P."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Majumder S."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Majumder S."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Mohler J.L."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Mohler J.L."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Parker C.E."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Parker C.E."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Warren M.R."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Warren M.R."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Whang Y.E."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/author | "Whang Y.E."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/17494760 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |