Cross Talk between Protein Kinase A and Androgen Signaling Pathway

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Authors

  • Amity Institute of Biotechnology, Amity University, Gurgaon 122413, Haryana ,IN
  • Amity Institute of Biotechnology, Amity University, Gurgaon 122413, Haryana ,IN

DOI:

https://doi.org/10.18311/jer/2015/v19/86041

Keywords:

Androgen Signaling, Non-Genomic Signaling, Prostate Cancer, Protein Kinase A.
Biochemistry

Abstract

Protein kinases are enzymes that add phosphate group to proteins to modify their function. These proteins regulate signal transduction pathways, essential for many biological processes such as cell cycle, cell signaling, protein and enzyme regulation, etc. There are 518 protein kinases, divided in to 7 main families. Protein kinase A (PKA) is a member of AGC family of protein kinases. It is activated by activation of G protein-coupled receptors (GPCR) and plays an important role in many cellular pathways including androgen signaling. Steroid hormones such as androgens primarily function through a genomic pathway, binding to cytosolic androgen receptors (AR) and initiating changes in transcription of target genes. Androgens also functions through a non-genomic pathway which is rapid and mediated by membrane receptors. It manifests its effects by activation of cellular signal transduction pathways such as PKA, Protein kinase C, and mitogen activated kinase, and does not involve transcription. In this review, we have analyzed the interaction between androgen signaling pathways and PKA, and have highlighted how each of these pathways complements and strengthens the function of the other. PKA plays an important role in complete activation of nuclear AR and in turn PKA can be activated by androgens. The complex interaction between the two pathways plays a critical role in development and progression of prostate cancer (PCa). Though the exact role of each pathway is not completely understood yet simultaneous inhibition of both pathways could prove to be beneficial for PCa patients.

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Published

2015-06-01

How to Cite

Dagar, M., & Bhattacharjee, G. B. (2015). Cross Talk between Protein Kinase A and Androgen Signaling Pathway. Journal of Endocrinology and Reproduction, 19(1), 1–6. https://doi.org/10.18311/jer/2015/v19/86041

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Section

Review Article

 

References

Anscher MS. (2004) Salvage radiotherapy for recurrent prostate cancer. J Am Med Assoc. 291: 1380-1382.

Bagchi G, Wu J, French J, et al. (2008) Androgens transduce the G alphas-mediated activation of protein kinase A in prostate cells. Cancer Res 68: 3225-3231.

Benten WPM, Lieberherr M, Giese G, et al. (1999) Functional testosterone receptors in plasma membranes of T cells. FASEB J 13: 123–133.

Ceballos G, Figueroa L, Rubio I, et al. (1999) Acute and non-genomic effects of testosterone on isolated and perfused rat heart. J Cardiovasc Pharmacol. 33: 691–697.

Cheetham GM. (2004) Novel protein kinases and molecular mechanisms of autoinhibition. Curr Opin Struct Biol. 14: 700-705.

Chou TM, Sudhir K, Hutchison SJ, et al. (1996) Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo. Circulation 94: 2614–2619.

Costarella CE, Stallone JN, Rutecki GK, Whittier FC. (1996) Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Exp Ther. 277: 34–39.

Culig Z, Klocker H, Bartsch G, Hobisch A. (2002) Androgen receptors in prostate cancer. Endocrine-Related Cancer 9: 155–170.

Desiniotis A, Schafer G, Klocker H, Eder IE. (2010) Enhanced antiproliferative and proapoptotic effects on prostate cancer cells by simultaneously inhibiting androgen receptor and cAMP-dependent protein kinase A. Int J Cancer 126: 775–789.

de Winter RJA, Janssen PJ, Sleddens HM, et al. (1994) Androgen receptor status in localized and locally progressive hormone refractory human prostate cancer. Am J Pathol. 144: 735–746.

Eder IE, Egger M, Neuwirt H, et al. (2013) Enhanced inhibition of Prostate tumor growth by dual targeting the androgen receptor and the regulatory subunit type Iα of protein kinase A in vivo. Int J Mol Sci. 14: 11942-11962.

Feldman BJ, Feldman D. (2001) The development of androgen-independent prostate cancer. Nat Rev Cancer 1: 34-45.

Gorczynska E, Handelsman DJ. (1995) Androgens rapidly increase the cytosolic calcium concentration in Sertoli cells. Endocrinology 136: 2052-2059.

Heinlein CA, Chang C. (2002) The roles of androgen receptors and androgen-binding proteins in non-genomic androgen actions. Mol Endrocrinol. 16: 2181-2187.

Jemal A, Murray T, Ward E, et al. (2005) Cancer statistics. CA Cancer J Clin. 55: 10–30.

Kim J, Jia l, Stallcup MR, Coetzee GA (2005) The role of protein kinase A pathway and cAMP responsive elementbinding protein in androgen receptor-mediated transcription at the prostate-specific antigen locus. J Mol Endocrinol 34:107–118.

Kondapalli L, Soltani K, Lacouture ME. (2005) The promise of molecular targeted therapies: protein kinase inhibitors in the treatment of cutaneous malignancies. J Am Acad Dermatol. 53: 291-302.

Kasbohm EA, Guo R, Yowell CW et al. (2005) Androgen receptor activation by Gs signaling in prostate cancer cells. J Biol Chem 280: 11583-11589.

Lee DK, Chang C. (2003) Molecular communication between androgen receptor and general transcription machinery. J Steroid Biochem Mol Biol. 84: 41-49.

Lieberherr M, Grosse B. (1994) Androgens increase intracellular calcium concentration and inositol 1.4.5-triphosphate and diacylglycerol formation via a pertussis toxin-sensitive G-protein. J Biol Chem. 269: 7217-7223.

Manning G, Whyte DB, Martinez R et al. (2002) The protein kinase complement of the human genome. Science 298: 1912-1934.

Nazareth LV, Weigel NL. (1996) Activation of the human androgen receptor through a protein kinase A signaling pathway. J Biol Chem. 271: 19900–19907.

Rubio-Gayosso I, Garcia-Ramirez O, Gutierrez-Serdan R et al. (2002) Testosterone inhibits bradykinin-induced intracellular calcium kinetics in rat aortic endothelial cells in culture. Steroids 67: 393–397.

Sadar MD (1999) Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. J Biol Chem. 274: 7777-7783.

Sadar MD, Hussain M, Bruchovsky N. (1999) Prostate cancer: Molecular biology of early progression to androgen independence. Endocr Relat Cancer 6: 487–502.

Sarwar M, Sandberg S , Abrahamsson P-A, , Persson JL. (2014) Protein kinase A (PKA) pathway is functionally linked to androgen receptor (AR) in the progression of prostate cancer. Urol Oncol Sem Orig Invest 32: 25.e1–12.

Tasken K, Aandahl EM. (2004) Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev. 84: 137–167.

Taylor SS, Kim CW, Cheng CY et al. (2002) Fifty years since the discovery of PKA. The FASEB J 22: 412-413.

Wang G, Jones SJM, Marra MA, Sadar MD. (2006) Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene 25: 7311–7323.

Yue P, Chatterjee K, Beale C et al. (1995) Testosterone relaxes rabbit coronary arteries and aorta. Circulation 91: 1154–1160.

Zylinska L, Gromadzinska E, Lachowicz L. (1999) Short-time effects of neuroactive steroids on rat cortical Ca2+-ATPase activity. Biochim Biophys Acta 1437:257-264.