Suppression of Androgen Receptor Transactivation by Pyk2 via Interaction and Phosphorylation of the ARA55 Coregulator*

The proline-rich tyrosine kinase 2 (Pyk2) was first identified as a key kinase linked to the MAP kinase and JNK signaling pathways that play important roles in cell growth and adhesion. The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer progression, however, remains unclear. Here we report that using the full-length androgen receptor-associated protein, ARA55, coregulator as bait, we were able to isolate an ARA55-interacting protein, Pyk2, and demonstrated that Pyk2 could repress AR transactivation via inactivation of ARA55. This inactivation may result from the direct phosphorylation of ARA55 by Pyk2 at tyrosine 43, impairing the coactivator activity of ARA55 and/or sequestering ARA55 to reduce its interaction with AR. Our finding that Pyk2 can indirectly modulate AR function via interaction and/or phosphorylation of ARA55 not only expands the role of Pyk2 in AR-mediated prostate cancer growth but also strengthens the role of ARA55 as an AR coregulator.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-05-03

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M111218200PMID 11856738
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Identification and characterization of androgen receptor associated coregulators in prostate cancer cells.

  2001cited by this paper
• Different expression of androgen receptor coactivators in human prostate.

  2001cited by this paper
• Variations of Proline-Rich Kinase Pyk2 Expression Correlate with Prostate Cancer Progression

  2001cited by this paper
• Identification and characterization of a novel androgen receptor coregulator ARA267-alpha in prostate cancer cells.

  2001cited by this paper
• Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor

  2001cited by this paper
• Identification and Characterization of a Novel Androgen Receptor Coregulator ARA267-α in Prostate Cancer Cells*

  2001cited by this paper
• Phosphorylation of Steroid Receptor Coactivator-1

  2000cited by this paper
• RAFTK/Pyk2-mediated cellular signalling.

  2000cited by this paper
• Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells.

  2000cited by this paper
• AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor

  2000cited by this paper
• Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix.

  2000cited by this paper
• Nuclear receptor coregulators: cellular and molecular biology.

  1999cited by this paper
• Isolation and Characterization of ARA160 as the First Androgen Receptor N-terminal-associated Coactivator in Human Prostate Cells*

  1999cited by this paper
• Protein tyrosine kinase Pyk2 mediates the Jak-dependent activation of MAPK and Stat1 in IFN-gamma, but not IFN-alpha, signaling.

  1999cited by this paper
• Cloning and Characterization of Androgen Receptor Coactivator, ARA55, in Human Prostate*

  1999cited by this paper
• Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1.

  1999cited by this paper
• Efficient control of tetracycline-responsive gene expression from an autoregulated bi-directional expression vector.

  1999cited by this paper
• From HER2/Neu signal cascade to androgen receptor and its coactivators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells.

  1999cited by this paper
• Protein tyrosine kinase Pyk2 mediates the Jak‐dependent activation of MAPK and Stat1 in IFN‐γ, but not IFN‐α, signaling

  1999cited by this paper
• The Linkage of Kennedy’s Neuron Disease to ARA24, the First Identified Androgen Receptor Polyglutamine Region-associated Coactivator*

  1999cited by this paper
• Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: integration of hormone signaling in reproduction and stress.

  1999cited by this paper
• Differential Regulation of Pyk2 and Focal Adhesion Kinase (FAK)

  1998cited by this paper
• Regulation of a Calcium-dependent Tyrosine Kinase in Vascular Smooth Muscle Cells by Angiotensin II and Platelet-derived Growth Factor

  1998cited by this paper
• Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.

  1998cited by this paper
• Tyrosine Phosphorylation of the Related Adhesion Focal Tyrosine Kinase in Megakaryocytes upon Stem Cell Factor and Phorbol Myristate Acetate Stimulation and Its Association with Paxillin*

  1997cited by this paper
• Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells.

  1996cited by this paper
• Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes.

  1996cited by this paper
• A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation

  1996cited by this paper
• Activation of the Human Androgen Receptor through a Protein Kinase A Signaling Pathway*

  1996cited by this paper
• Protection from Natural Killer Cell-Mediated Lysis by HLA-G Expression on Target Cells

  1996cited by this paper
• Activation of Pyk2 by Stress Signals and Coupling with JNK Signaling Pathway

  1996cited by this paper
• Androgen receptor: an overview.

  1995cited by this paper
• Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions

  1995cited by this paper
• Characterization of the TGF beta 1-inducible hic-5 gene that encodes a putative novel zinc finger protein and its possible involvement in cellular senescence.

  1994cited by this paper
• Identification of 3',5'-cyclic adenosine monophosphate response element and other cis-acting elements in the human androgen receptor gene promoter.

  1994cited by this paper
• Molecular cloning of human and rat complementary DNA encoding androgen receptors.

  1988cited by this paper

• The impact, mechanisms and prevention strategies of environmental endocrine disruptors on male reproductive health

  2025cites this paper
• Reduced Proline-Rich Tyrosine Kinase 2 Promotes Tumor Metastasis by Activating Epithelial–Mesenchymal Transition in Colorectal Cancer

  2024cites this paper
• Nuclear Receptor Coregulators in Hormone-Dependent Cancers

  2022cites this paper
• The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases

  2021cites this paper
• Analyse protéomique des réseaux de signalisation du récepteur aux androgènes modulés par l'Enzalutamide dans le cancer de la prostate résistant à la castration

  2019cites this paper
• Role of Pyk2 in Human Cancers

  2018cites this paper
• An emerging link between LIM domain proteins and nuclear receptors

  2018cites this paper
• Glucocorticoid receptor binding to chromatin is selectively controlled by the coregulator Hic-5 and chromatin remodeling enzymes

  2017cites this paper
• PYK 2 via S 6 K 1 regulates the function of androgen receptors and the growth of prostate cancer cells

  2016cites this paper
• PYK2 via S6K1 regulates the function of androgen receptors and the growth of prostate cancer cells.

  2016cites this paper
• TMPRSS2 promoter driven enzyme-prodrug therapy for the treatment of PCa

  2015cites this paper
• Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

  2015cites this paper
• Nonreceptor Tyrosine Kinases in Prostate

  2014cites this paper
• Nuclear Matrix Proteins in Disparity of Prostate Cancer

  2011cites this paper
• The roles of Hic-5 in BMP signaling in prostate cancer cells and generation of knockout mouse model

  2011cites this paper
• Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

  2010cites this paper
• La voie ERK1/2 : point d’intégration et de convergence des connexions entre voies de signalisation dans les cellules épithéliales de prostate normale

  2010cites this paper
• Androgen Receptor Biology in Prostate Cancer

  2010cites this paper
• Amplification and co-regulators of androgen receptor gene in prostate cancer.

  2009cites this paper
• Pyk2 and Cyr61 at the cross-road of cAMP-dependent signalling in invasiveness and neuroendocrine differentiation of prostate cancer

  2009cites this paper
• Key Roles of TGF-β and Smad3 in Prostate Cancer

  2008cites this paper
• Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55

  2008cites this paper
• Leupaxin, a novel coactivator of the androgen receptor, is expressed in prostate cancer and plays a role in adhesion and invasion of prostate carcinoma cells.

  2008cites this paper
• Non-genomic actions of androgens.

  2008cites this paper
• The Roles of a LIM Domain Protein, Hic-5/ARA55, in TGF-β Signaling in Prostate Cancer Cells

  2008cites this paper
• ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

  2007cites this paper
• Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex.

  2007cites this paper
• Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells.

  2007cites this paper
• Androgen receptor coregulators and their involvement in the development and progression of prostate cancer

  2007cites this paper
• Nonreceptor tyrosine kinases in prostate cancer.

  2007cites this paper
• Gonadotropin-Releasing Hormone Functionally Antagonizes Testosterone Activation of the Human Androgen Receptor in Prostate Cells through Focal Adhesion Complexes Involving Hic-5

  2007cites this paper
• Suppression of androgen receptor transactivation and prostate cancer cell growth by heterogeneous nuclear ribonucleoprotein A1 via interaction with androgen receptor coregulator ARA54.

  2007cites this paper
• Roles of androgen-dependent and -independent activation of signal transduction pathways for cell proliferation of prostate cancer cells

  2007cites this paper
• Androgen receptor corepressors and prostate cancer.

  2006influential citation
• ERK8 Down-regulates Transactivation of the Glucocorticoid Receptor through Hic-5*

  2006cites this paper
• Molecular cloning and identification of mouse Cklfsf2a and Cklfsf2b, two homologues of human CKLFSF2.

  2006cites this paper
• [Molecular biology in the prostate neoplasia].

  2005cites this paper
• Novel Function of Androgen Receptor-associated Protein 55/Hic-5 as a Negative Regulator of Smad3 Signaling*

  2005cites this paper
• Identification and analysis of Hic‐5/ARA55 isoforms: Implications for integrin signaling and steroid hormone action

  2005cites this paper
• Tyrosine-phosphorylated Hic-5 inhibits epidermal growth factor-induced lamellipodia formation.

  2005cites this paper
• Biologia molecular das neoplasias de próstata

  2005cites this paper
• The androgen receptor and signal‐transduction pathways in hormone‐refractory prostate cancer. Part 2: androgen‐receptor cofactors and bypass pathways

  2005cites this paper
• Peptidyl-Prolyl Isomerase 1 (Pin1) Serves as a Coactivator of Steroid Receptor by Regulating the Activity of Phosphorylated Steroid Receptor Coactivator 3 (SRC-3/AIB1)

  2005cites this paper
• atualização Biologia Molecular das Neoplasias de Próstata

  2005cites this paper
• Mechanism of p21-activated Kinase 6-mediated Inhibition of Androgen Receptor Signaling*

  2004cites this paper
• Androgen receptor in prostate cancer.

  2004cites this paper
• Androgen Receptor Coregulators in Prostate Cancer

  2004cites this paper
• Paxillin: adapting to change.

  2004cites this paper
• Coregulator function: a key to understanding tissue specificity of selective receptor modulators.

  2004cites this paper
• Androgens and ovarian cancers.

  2004cites this paper
• Prostate cancer and the met hepatocyte growth factor receptor.

  2004cites this paper
• Antidepressant effect of the calcium-activated tyrosine kinase Pyk2 in the lateral septum.

  2003cites this paper
• The Use of Phage Display Technique for the Isolation of Androgen Receptor Interacting Peptides with (F/W)XXL(F/W) and FXXLY New Signature Motifs*

  2003cites this paper
• Recent advances in androgen receptor action

  2003cites this paper
• The Scaffolding Protein RACK1 Interacts with Androgen Receptor and Promotes Cross-talk through a Protein Kinase C Signaling Pathway*

  2003cites this paper
• Identification of a Novel Testicular Orphan Receptor-4 (TR4)-associated Protein as Repressor for the Selective Suppression of TR4-mediated Transactivation*

  2003cites this paper
• Inactivation of androgen receptor coregulator ARA55 inhibits androgen receptor activity and agonist effect of antiandrogens in prostate cancer cells

  2003cites this paper
• Expression of androgen receptor coactivators in normal and cancer prostate tissues and cultured cell lines

  2003cites this paper
• The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions.

  2002cites this paper
• Proteasome Activity Is Required for Androgen Receptor Transcriptional Activity via Regulation of Androgen Receptor Nuclear Translocation and Interaction with Coregulators in Prostate Cancer Cells*

  2002cites this paper
• Journal of Steroid Biochemistry and Molecular Biology Actin Associated Proteins Function as Androgen Receptor Coregulators: an Implication of Androgen Receptor's Roles in Skeletal Muscle

  year unknowncites this paper