Androgen Receptor Specifically Interacts with a Novel p21-activated Kinase, PAK6

The androgen receptor (AR) is a hormone-dependent transcription factor that plays important roles in male sexual differentiation and development. Transcription activation by steroid hormone receptors, such as the androgen receptor, is mediated through interaction with cofactors. We recently identified a novel AR-interacting protein, provisionally termed PAK6, that shares a high degree of sequence similarity with p21-activated kinases (PAKs). PAK6 is a 75-kDa protein that contains a putative amino-terminal Cdc42/Rac interactive binding motif and a carboxyl-terminal kinase domain. A domain-specific and ligand-dependent interaction between AR and PAK6 was further confirmed in vivo and in vitro. Northern blot analysis revealed that PAK6 is highly expressed in testis and prostate tissues. Most importantly, immunofluorescence studies showed that PAK6 cotranslocates into the nucleus with AR in response to androgen. Transient transfection experiments showed that PAK6 specifically repressed AR-mediated transcription. This report identifies a novel function for a PAK-homologous protein and suggests a potential unique mechanism by which other signal transduction pathways may cross-talk with AR pathways to regulate AR function in normal and malignant prostate cells.AF276893 The androgen receptor (AR) is a hormone-dependent transcription factor that plays important roles in male sexual differentiation and development. Transcription activation by steroid hormone receptors, such as the androgen receptor, is mediated through interaction with cofactors. We recently identified a novel AR-interacting protein, provisionally termed PAK6, that shares a high degree of sequence similarity with p21-activated kinases (PAKs). PAK6 is a 75-kDa protein that contains a putative amino-terminal Cdc42/Rac interactive binding motif and a carboxyl-terminal kinase domain. A domain-specific and ligand-dependent interaction between AR and PAK6 was further confirmed in vivo and in vitro. Northern blot analysis revealed that PAK6 is highly expressed in testis and prostate tissues. Most importantly, immunofluorescence studies showed that PAK6 cotranslocates into the nucleus with AR in response to androgen. Transient transfection experiments showed that PAK6 specifically repressed AR-mediated transcription. This report identifies a novel function for a PAK-homologous protein and suggests a potential unique mechanism by which other signal transduction pathways may cross-talk with AR pathways to regulate AR function in normal and malignant prostate cells.AF276893 androgen receptor ligand binding domain androgen response element androgen receptor-associated DNA binding domain p21-activated kinase Cdc42/Racinteractive binding transcription activation domain β-galactosidase rapid amplification of 5′ cDNA ends mouse mammary tumor virus glucocorticoid receptor glutathione S-transferase SDS-polyacrylamide gel electrophoresis dihydrotestosterone Sabouraud dextrose The effects of androgens are mediated by the androgen receptor (AR),1 which plays a critical role in inducing normal differentiation of tissues of the reproductive organs and in the development and progression of prostate cancer (1Quigley C.A. De Bellis A. Marschke K.B. el-Awady M.K. Wilson E.M. French F.S. Endocr. Rev. 1995; 16: 271-321Crossref PubMed Google Scholar). AR belongs to the nuclear receptor superfamily, whose members regulate ligand-dependent gene transcription (2Tsai M.J. O'Malley B.W. Annu. Rev. Biochem. 1994; 63: 451-486Crossref PubMed Scopus (2678) Google Scholar, 3Horwitz K.B. Jackson T.A. Bain D.L. Richer J.K. Takimoto G.S. Tung L. Mol. Endocrinol. 1996; 10: 1167-1177Crossref PubMed Scopus (834) Google Scholar). The AR and other receptors in this family possess identifiable activation domains that confer transactivation potential when fused to a heterologous DNA binding domain. However, an important feature of the AR and other nuclear receptors that distinguish them from other transcription factors is that they are activated by their ligand binding domains (LBD). The unbound AR forms a complex with heat-shock proteins (HSPs) (4Sanchez E.R. Faber L.E. Henzel W.J. Pratt W.B. Biochemistry. 1990; 29: 5145-5152Crossref PubMed Scopus (164) Google Scholar, 5Sullivan W.P. Vroman B.T. Bauer V.J. J. Steroid Biochem. Mol. Biol. 1992; 43: 37-41Crossref PubMed Scopus (21) Google Scholar). Upon binding to ligand, the AR dissociates from the HSPs and translocates into the nucleus, where it binds to the androgen response element (ARE) and recruits cofactors to regulate transcription (6Jenster G. Semin. Oncol. 1999; 26: 407-421PubMed Google Scholar,7Jenster G. van der Korput H.A. van Vroonhoven C. van der Kwast T.H. Trapman J. Brinkmann A.O. Mol. Endocrinol. 1991; 5: 1396-1404Crossref PubMed Scopus (417) Google Scholar).Several coactivators that interact preferentially with the LBD of nuclear receptors have been identified, such as SRC1/NCoA1, TIF2/GRIP1/NCoA2, and ACTR/AIB1/TRAM1/RAC3 (8Halachmi S. Marden E. Martin G. MacKay H. Abbondanza C. Brown M. Science. 1994; 264: 1455-1458Crossref PubMed Scopus (565) Google Scholar, 9Onate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1995; 270: 1354-1357Crossref PubMed Scopus (2042) Google Scholar, 10Cavailles V. Dauvois S. L'Horset F. Lopez G. Hoare S. Kushner P.J. Parker M.G. EMBO J. 1995; 14: 3741-3751Crossref PubMed Scopus (670) Google Scholar, 11Hong H. Kohli K. Trivedi A. Johnson D.L. Stallcup M.R. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4948-4952Crossref PubMed Scopus (611) Google Scholar). These cofactors facilitate nuclear receptor-mediated, ligand-dependent transcription through chromatin remodeling and histone modification (12Xu L. Glass C.K. Rosenfeld M.G. Curr. Opin. Genet. Dev. 1999; 9: 140-147Crossref PubMed Scopus (808) Google Scholar). A group of AR-associated (ARA) proteins, termed ARA54 (13Kang H.Y. Yeh S. Fujimoto N. Chang C. J. Biol. Chem. 1999; 274: 8570-8576Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar), ARA55 (14Fujimoto N. Yeh S. Kang H.Y. Inui S. Chang H.C. Mizokami A. Chang C. J. Biol. Chem. 1999; 274: 8316-8321Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar), ARA70 (15Yeh S. Chang C. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 5517-5521Crossref PubMed Scopus (529) Google Scholar), Tip60 (16Brady M.E. Ozanne D.M. Gaughan L. Waite I. Cook S. Neal D.E. Robson C.N. J. Biol. Chem. 1999; 274: 17599-17604Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar), and HBO1 (17Sharma M. Zarnegar M. Li X. Lim B. Sun Z. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google was identified by the and LBD of AR as in a and to the ligand-dependent transactivation of is a novel AR-interacting protein that was identified recently by a and was to AR-mediated transcription U. E. A. M. A. C. EMBO J. PubMed Scopus Google been that factors that protein kinase A steroid hormone receptors in the of ligand have a with ligand Trapman J. Brinkmann A.O. Mol. Endocrinol. 1995; PubMed Scopus Google Scholar, J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of protein kinase A the AR J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, M. Wilson E.M. 1994; Google Scholar). activation of the AR by the factors factor factor and factor been Z. A. C. Trapman J. A. G. H. 1994; Google Scholar). These that the AR to a of proteins and that pathways may AR in normal and tumor p21-activated kinases are members of a of protein by a highly amino-terminal Cdc42/Racinteractive binding domain and a carboxyl-terminal kinase domain E. H. Lim L. 1994; PubMed Scopus Google Scholar, G. F. A. EMBO J. 1995; 14: PubMed Scopus Google Scholar, S. J. Science. 1995; PubMed Scopus Google Scholar, S. L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). and are members of the the recently members and high with other have to J. Biochem. Biol. PubMed Scopus Google Scholar). The their effects by kinase protein kinase that the factor and to the nucleus that activation of the response protein and S. J. J. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google S. M.J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (164) Google Scholar). studies have that in this is mediated Cdc42/Rac of E. H. Lim L. 1994; PubMed Scopus Google Scholar, S. B. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). the of are in the of a of of the protein kinase and of J. Biochem. Biol. PubMed Scopus Google Scholar, A. S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. J. Biol. PubMed Scopus Google Scholar, C. S. Johnson J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google a identified a novel AR-interacting protein, provisionally termed PAK6, which shares a high degree of sequence similarity with family other PAK6 contains a putative amino-terminal domain and a carboxyl-terminal kinase domain. PAK6 is highly expressed in testis and prostate tissues. interaction between AR and PAK6 was further in and in PAK6 to with AR in a ligand-dependent of PAK6 with AR was to specifically AR-mediated transcription. These a novel function for proteins and a unique mechanism by which other signal transduction such as the may AR-mediated this identified a p21-activated PAK6, and a interaction between PAK6 and These to the steroid hormone receptor a novel function for this AR-interacting proteins have been identified and in they are transcription factors that roles in transcription. The of PAK6, a protein as an AR-interacting protein is and have a of to that the interaction between PAK6 and AR is a We showed that the LBD of AR is and for the interaction with PAK6 in an in the that in the LBD of AR binding to ligand are for PAK6 to to AR The interaction was further confirmed in vivo in the the AR protein specifically with The interaction between AR and PAK6 proteins was in the in which PAK6 with AR in the transcription androgen was for the a interaction between AR and PAK6 in the immunofluorescence in PAK6 cotranslocates into with AR in response to androgen the that the interaction between AR and PAK6 is for the of the interaction between PAK6 and PAK6 was to AR-mediated transcription. transfection showed that PAK6 AR-mediated PAK6 was to have steroid hormone receptor, the These that the of AR by PAK6 may of the of their the it to PAK6 with other nuclear and between PAK6 and AR have been the mechanism by which PAK6 AR function is the that PAK6 contains a carboxyl-terminal kinase PAK6 AR by the of AR AR proteins, to of AR by PAK6 studies have that AR AR transcription U. H. Mol. Biol. 9: PubMed Scopus Google Scholar, Wilson E.M. Mol. Endocrinol. 1995; 9: PubMed Google Scholar). have that of AR AR transactivation M. C. J. L. V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). it that the of AR-mediated transcription by PAK6 may to an of AR the mechanism by which PAK6 fused PAK6 into a heterologous DNA binding domain to and PAK6 carboxyl-terminal showed These are with the protein of PAK6, that PAK6 may a domain may with the of other transcription AR coactivators have been to AR-mediated transcription through a interaction with the LBD of mechanism for PAK6 of AR to with the binding of the coactivators to this is that of the AR the of AR by PAK6 the mechanism of ARA70 of AR transactivation is further with other AR coactivators to to the of PAK6 have that PAK6 AR the protein sequence and of PAK6 that the protein may possess other with other a that PAK6 is expressed in testis and This unique is to that of from other members A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). for and which have been to expressed in other to expressed in tissues A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar, J. Biochem. Biol. PubMed Scopus Google Scholar). The of PAK6 in testis and prostate tissues is with the interaction between AR and PAK6 that have which further the that PAK6 plays a potential role in AR These the that signal proteins are the of the family of and The to a binding as their kinase by a mechanism J. Biochem. Biol. PubMed Scopus Google Full Text Full Text PDF PubMed Scopus Google Scholar). analysis showed that PAK6 contains and kinase domains that are to the other to and However, of PAK6 from sequence with and the of it that the mechanism of of PAK6 may from other PAK6 was to interact with activated through PAK6 kinase was activated binding to This the as to other family members specifically PAK6 PAK6 in interact with members of the family in studies have that the domain of with domain to the kinase by a and H. M. Mol. Biol. 1999; PubMed Scopus Google Scholar). We have that the PAK6 kinase the carboxyl-terminal kinase that a mechanism for kinase may in are to in the was to from the to with activated A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). that PAK6 cotranslocates into the nucleus with AR suggests that PAK6 may have a novel function other to AR PAK6 through their of PAK6 interaction with AR this for the that a novel protein, PAK6, specifically with Most importantly, the a mechanism AR pathways cross-talk with pathways of the studies of the of AR-mediated transcription by PAK6 may into the of normal prostate and prostate The effects of androgens are mediated by the androgen receptor (AR),1 which plays a critical role in inducing normal differentiation of tissues of the reproductive organs and in the development and progression of prostate cancer (1Quigley C.A. De Bellis A. Marschke K.B. el-Awady M.K. Wilson E.M. French F.S. Endocr. Rev. 1995; 16: 271-321Crossref PubMed Google Scholar). AR belongs to the nuclear receptor superfamily, whose members regulate ligand-dependent gene transcription (2Tsai M.J. O'Malley B.W. Annu. Rev. Biochem. 1994; 63: 451-486Crossref PubMed Scopus (2678) Google Scholar, 3Horwitz K.B. Jackson T.A. Bain D.L. Richer J.K. Takimoto G.S. Tung L. Mol. Endocrinol. 1996; 10: 1167-1177Crossref PubMed Scopus (834) Google Scholar). The AR and other receptors in this family possess identifiable activation domains that confer transactivation potential when fused to a heterologous DNA binding domain. However, an important feature of the AR and other nuclear receptors that distinguish them from other transcription factors is that they are activated by their ligand binding domains (LBD). The unbound AR forms a complex with heat-shock proteins (HSPs) (4Sanchez E.R. Faber L.E. Henzel W.J. Pratt W.B. Biochemistry. 1990; 29: 5145-5152Crossref PubMed Scopus (164) Google Scholar, 5Sullivan W.P. Vroman B.T. Bauer V.J. J. Steroid Biochem. Mol. Biol. 1992; 43: 37-41Crossref PubMed Scopus (21) Google Scholar). Upon binding to ligand, the AR dissociates from the HSPs and translocates into the nucleus, where it binds to the androgen response element (ARE) and recruits cofactors to regulate transcription (6Jenster G. Semin. Oncol. 1999; 26: 407-421PubMed Google Scholar,7Jenster G. van der Korput H.A. van Vroonhoven C. van der Kwast T.H. Trapman J. Brinkmann A.O. Mol. Endocrinol. 1991; 5: 1396-1404Crossref PubMed Scopus (417) Google Scholar). coactivators that interact preferentially with the LBD of nuclear receptors have been identified, such as SRC1/NCoA1, TIF2/GRIP1/NCoA2, and ACTR/AIB1/TRAM1/RAC3 (8Halachmi S. Marden E. Martin G. MacKay H. Abbondanza C. Brown M. Science. 1994; 264: 1455-1458Crossref PubMed Scopus (565) Google Scholar, 9Onate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1995; 270: 1354-1357Crossref PubMed Scopus (2042) Google Scholar, 10Cavailles V. Dauvois S. L'Horset F. Lopez G. Hoare S. Kushner P.J. Parker M.G. EMBO J. 1995; 14: 3741-3751Crossref PubMed Scopus (670) Google Scholar, 11Hong H. Kohli K. Trivedi A. Johnson D.L. Stallcup M.R. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4948-4952Crossref PubMed Scopus (611) Google Scholar). These cofactors facilitate nuclear receptor-mediated, ligand-dependent transcription through chromatin remodeling and histone modification (12Xu L. Glass C.K. Rosenfeld M.G. Curr. Opin. Genet. Dev. 1999; 9: 140-147Crossref PubMed Scopus (808) Google Scholar). A group of AR-associated (ARA) proteins, termed ARA54 (13Kang H.Y. Yeh S. Fujimoto N. Chang C. J. Biol. Chem. 1999; 274: 8570-8576Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar), ARA55 (14Fujimoto N. Yeh S. Kang H.Y. Inui S. Chang H.C. Mizokami A. Chang C. J. Biol. Chem. 1999; 274: 8316-8321Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar), ARA70 (15Yeh S. Chang C. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 5517-5521Crossref PubMed Scopus (529) Google Scholar), Tip60 (16Brady M.E. Ozanne D.M. Gaughan L. Waite I. Cook S. Neal D.E. Robson C.N. J. Biol. Chem. 1999; 274: 17599-17604Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar), and HBO1 (17Sharma M. Zarnegar M. Li X. Lim B. Sun Z. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google was identified by the and LBD of AR as in a and to the ligand-dependent transactivation of is a novel AR-interacting protein that was identified recently by a and was to AR-mediated transcription U. E. A. M. A. C. EMBO J. PubMed Scopus Google Scholar). been that factors that protein kinase A steroid hormone receptors in the of ligand have a with ligand Trapman J. Brinkmann A.O. Mol. Endocrinol. 1995; PubMed Scopus Google Scholar, J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of protein kinase A the AR J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, M. Wilson E.M. 1994; Google Scholar). activation of the AR by the factors factor factor and factor been Z. A. C. Trapman J. A. G. H. 1994; Google Scholar). These that the AR to a of proteins and that pathways may AR in normal and tumor The p21-activated kinases are members of a of protein by a highly amino-terminal Cdc42/Racinteractive binding domain and a carboxyl-terminal kinase domain E. H. Lim L. 1994; PubMed Scopus Google Scholar, G. F. A. EMBO J. 1995; 14: PubMed Scopus Google Scholar, S. J. Science. 1995; PubMed Scopus Google Scholar, S. L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). and are members of the the recently members and high with other have to J. Biochem. Biol. PubMed Scopus Google Scholar). The their effects by kinase protein kinase that the factor and to the nucleus that activation of the response protein and S. J. J. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google S. M.J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (164) Google Scholar). studies have that in this is mediated Cdc42/Rac of E. H. Lim L. 1994; PubMed Scopus Google Scholar, S. B. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). the of are in the of a of of the protein kinase and of J. Biochem. Biol. PubMed Scopus Google Scholar, A. S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. J. Biol. PubMed Scopus Google Scholar, C. S. Johnson J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). a identified a novel AR-interacting protein, provisionally termed PAK6, which shares a high degree of sequence similarity with family other PAK6 contains a putative amino-terminal domain and a carboxyl-terminal kinase domain. PAK6 is highly expressed in testis and prostate tissues. interaction between AR and PAK6 was further in and in PAK6 to with AR in a ligand-dependent of PAK6 with AR was to specifically AR-mediated transcription. These a novel function for proteins and a unique mechanism by which other signal transduction such as the may AR-mediated transcription. this identified a p21-activated PAK6, and a interaction between PAK6 and These to the steroid hormone receptor a novel function for this AR-interacting proteins have been identified and in they are transcription factors that roles in transcription. The of PAK6, a protein as an AR-interacting protein is and have a of to that the interaction between PAK6 and AR is a We showed that the LBD of AR is and for the interaction with PAK6 in an in the that in the LBD of AR binding to ligand are for PAK6 to to AR The interaction was further confirmed in vivo in the the AR protein specifically with The interaction between AR and PAK6 proteins was in the in which PAK6 with AR in the transcription androgen was for the a interaction between AR and PAK6 in the immunofluorescence in PAK6 cotranslocates into with AR in response to androgen the that the interaction between AR and PAK6 is for the of the interaction between PAK6 and PAK6 was to AR-mediated transcription. transfection showed that PAK6 AR-mediated PAK6 was to have steroid hormone receptor, the These that the of AR by PAK6 may of the of their the it to PAK6 with other nuclear and between PAK6 and AR have been the mechanism by which PAK6 AR function is the that PAK6 contains a carboxyl-terminal kinase PAK6 AR by the of AR AR proteins, to of AR by PAK6 studies have that AR AR transcription U. H. Mol. Biol. 9: PubMed Scopus Google Scholar, Wilson E.M. Mol. Endocrinol. 1995; 9: PubMed Google Scholar). have that of AR AR transactivation M. C. J. L. V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). it that the of AR-mediated transcription by PAK6 may to an of AR the mechanism by which PAK6 fused PAK6 into a heterologous DNA binding domain to and PAK6 carboxyl-terminal showed These are with the protein of PAK6, that PAK6 may a domain may with the of other transcription AR coactivators have been to AR-mediated transcription through a interaction with the LBD of mechanism for PAK6 of AR to with the binding of the coactivators to this is that of the AR the of AR by PAK6 the mechanism of ARA70 of AR transactivation is further with other AR coactivators to to the of PAK6 have that PAK6 AR the protein sequence and of PAK6 that the protein may possess other with other a that PAK6 is expressed in testis and This unique is to that of from other members A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). for and which have been to expressed in other to expressed in tissues A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar, J. Biochem. Biol. PubMed Scopus Google Scholar). The of PAK6 in testis and prostate tissues is with the interaction between AR and PAK6 that have which further the that PAK6 plays a potential role in AR These the that signal proteins are the of the family of and The to a binding as their kinase by a mechanism J. Biochem. Biol. PubMed Scopus Google Full Text Full Text PDF PubMed Scopus Google Scholar). analysis showed that PAK6 contains and kinase domains that are to the other to and However, of PAK6 from sequence with and the of it that the mechanism of of PAK6 may from other PAK6 was to interact with activated through PAK6 kinase was activated binding to This the as to other family members specifically PAK6 PAK6 in interact with members of the family in studies have that the domain of with domain to the kinase by a and H. M. Mol. Biol. 1999; PubMed Scopus Google Scholar). We have that the PAK6 kinase the carboxyl-terminal kinase that a mechanism for kinase may in are to in the was to from the to with activated A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). that PAK6 cotranslocates into the nucleus with AR suggests that PAK6 may have a novel function other to AR PAK6 through their of PAK6 interaction with AR this for the that a novel protein, PAK6, specifically with Most importantly, the a mechanism AR pathways cross-talk with pathways of the studies of the of AR-mediated transcription by PAK6 may into the of normal prostate and prostate this identified a p21-activated PAK6, and a interaction between PAK6 and These to the steroid hormone receptor a novel function for this AR-interacting proteins have been identified and in they are transcription factors that roles in transcription. The of PAK6, a protein as an AR-interacting protein is and have a of to that the interaction between PAK6 and AR is a We showed that the LBD of AR is and for the interaction with PAK6 in an in the that in the LBD of AR binding to ligand are for PAK6 to to AR The interaction was further confirmed in vivo in the the AR protein specifically with The interaction between AR and PAK6 proteins was in the in which PAK6 with AR in the transcription androgen was for the a interaction between AR and PAK6 in the immunofluorescence in PAK6 cotranslocates into with AR in response to androgen the that the interaction between AR and PAK6 is for the of the interaction between PAK6 and PAK6 was to AR-mediated transcription. transfection showed that PAK6 AR-mediated PAK6 was to have steroid hormone receptor, the These that the of AR by PAK6 may of the of their the it to PAK6 with other nuclear and between PAK6 and AR have been the mechanism by which PAK6 AR function is the that PAK6 contains a carboxyl-terminal kinase PAK6 AR by the of AR AR proteins, to of AR by PAK6 studies have that AR AR transcription U. H. Mol. Biol. 9: PubMed Scopus Google Scholar, Wilson E.M. Mol. Endocrinol. 1995; 9: PubMed Google Scholar). have that of AR AR transactivation M. C. J. L. V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). it that the of AR-mediated transcription by PAK6 may to an of AR the mechanism by which PAK6 fused PAK6 into a heterologous DNA binding domain to and PAK6 carboxyl-terminal showed These are with the protein of PAK6, that PAK6 may a domain may with the of other transcription AR coactivators have been to AR-mediated transcription through a interaction with the LBD of mechanism for PAK6 of AR to with the binding of the coactivators to this is that of the AR the of AR by PAK6 the mechanism of ARA70 of AR transactivation is further with other AR coactivators to to the of PAK6 have that PAK6 AR the protein sequence and of PAK6 that the protein may possess other with other a that PAK6 is expressed in testis and This unique is to that of from other members A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). for and which have been to expressed in other to expressed in tissues A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar, J. Biochem. Biol. PubMed Scopus Google Scholar). The of PAK6 in testis and prostate tissues is with the interaction between AR and PAK6 that have which further the that PAK6 plays a potential role in AR These the that signal proteins are the of the family of and The to a binding as their kinase by a mechanism J. Biochem. Biol. PubMed Scopus Google Full Text Full Text PDF PubMed Scopus Google Scholar). analysis showed that PAK6 contains and kinase domains that are to the other to and However, of PAK6 from sequence with and the of it that the mechanism of of PAK6 may from other PAK6 was to interact with activated through PAK6 kinase was activated binding to This the as to other family members specifically PAK6 PAK6 in interact with members of the family in studies have that the domain of with domain to the kinase by a and H. M. Mol. Biol. 1999; PubMed Scopus Google Scholar). We have that the PAK6 kinase the carboxyl-terminal kinase that a mechanism for kinase may in are to in the was to from the to with activated A. J. C. A. V. B. A. EMBO J. PubMed Scopus Google Scholar). that PAK6 cotranslocates into the nucleus with AR suggests that PAK6 may have a novel function other to AR PAK6 through their of PAK6 interaction with AR this for the that a novel protein, PAK6, specifically with Most importantly, the a mechanism AR pathways cross-talk with pathways of the studies of the of AR-mediated transcription by PAK6 may into the of normal prostate and prostate We are for the from A. and We for and for and in this