Androgen receptor signaling pathway (Homo sapiens)

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Description

Androgens, mainly testosterone and 5alpha-dihydrotestosterone (DHT) play significant role in the growth and development of the male reproductive organs. These steroid hormones bring about their biological functions through their associations with Androgen receptor (AR), a 110 KDa ligand dependent transcription factor that falls under the group of nuclear receptor superfamily. DHT binds the receptor with high affinity compared to testosterone. The AR gene is located in the X chromosome at Xq11-12 site. AR is cytosolic protein, which in the ligand unbound state, is present as a complex with various Heat shock proteins primarily Hsp70, 90 and 56 as well as p23. Upon ligand binding, it dissociates from the complex. AR is found to be expressed in a number of tissues and cells including prostate, testis, seminal vescicle, epididymis, skin, skeletal muscle, cardiac muscle, liver and central nervous system. The protein has four functional domains- an N terminal domain (NTD), a DNA binding domain (DBD), a hinge region and a Ligand binding Domain (LBD). The DBD is a 658 amino acid residue region that has ZNF motifs which allows it bind to DNA. The rest of the domains are involved in dimerization and ligand binding. Two phosphorylation events are proposed to play very important role in the activation of the receptor upon ligand binding. The first phosphorylation event releases the ligand binding domain for hormone binding. The subsequent phosphorylation event is triggered upon hormone binding. Activated AR upon ligand binding undergoes conformational change to form a homodimer and interacts tightly with the Androgen Response Element (ARE). The androgen receptor is known to bind to many co-regulators at different time points and in different cell types. This DNA protein complex triggers the expression of various target genes that are associated with the male phenotype. Modulation of the AR activity is carried out by several transcription factors like ARA70, TR4, SRC family members and CBP/p300 and other associated proteins. FXXLF and WXXLF motifs containing coactivators such as the p160 members bind with the AF2 region of the Ligand Binding Domain of the AR. Androgen receptors are known to induce apoptosis under certain conditions. Various regulators that regulate androgen induced apoptosis include BRCA1 and Smad3 and Akt. Mutation in AR are also known to be associated in a number of diseases including spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease and Androgen Insensitivity syndrome (AIS). Abnormal amplification of the androgen gene as well as deregulation of AR gene expression have been shown to be associated with prostate cancer.


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If you use this pathway, you must cite following paper:

Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3.

Ontology Tags

 

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History

View all...
CompareRevisionActionTimeUserComment
72130view07:56, 25 October 2013Mkutmonadded datasource to SIN3A and PIAS2
71364view18:36, 17 October 2013MaintBotAutomated update of data sources
63142view19:17, 8 May 2013MaintBotUpdating GPML version
53243view19:04, 1 November 2012RobertbaertschAdd gene id to RLN1
47971view14:16, 23 April 2012NetPathModified description
47970view14:14, 23 April 2012NetPathModified description
44951view12:35, 6 October 2011MartijnVanIerselOntology Term : 'androgen signaling pathway' added !
44596view20:59, 21 September 2011KhanspersModified categories
44595view20:59, 21 September 2011KhanspersModified description
44594view20:58, 21 September 2011KhanspersUpdating content to NetSlim
44118view20:49, 24 August 2011KhanspersReverted to version '23:17, 1 March 2011' by Khanspers
44046view23:41, 22 August 2011KhanspersModified description
44045view23:39, 22 August 2011KhanspersUpdating pathway from NetSlim
41063view23:17, 1 March 2011MaintBotRemoved redundant pathway information and comments
35667view22:37, 12 February 2010AlexanderPicoModified description
35427view11:00, 12 February 2010AndraAdded references
35299view23:19, 11 February 2010NsalomonisModified description
20973view11:30, 14 November 2008MaintBot[[Pathway:Homo sapiens:Androgen-Receptor NetPath 2]] moved to [[Pathway:WP138]]: Moved to stable identifier
7902view13:46, 7 January 2008MaintBot[[Pathway:Human:Androgen-Receptor NetPath 2]] moved to [[Pathway:Homo sapiens:Androgen-Receptor NetPath 2]]: Renaming species
7576view16:01, 18 December 2007MaintBotfixed category names
7195view12:33, 4 November 2007MaintBotAdded categories to GPML
6294view22:17, 22 May 2007A.Pandeygpml file for [[Human:Androgen-Receptor_NetPath_2]]

External references

View all...
NameTypeDatabase referenceComment
CAV1Protein857 (Entrez Gene)
CREB1Protein1385 (Entrez Gene)
ARProtein367 (Entrez Gene)
BRCA1Protein672 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
KLK3Rna354 (Entrez Gene)
RAC1Protein5879 (Entrez Gene)
CTNNB1Protein1499 (Entrez Gene)
CDC42Protein998 (Entrez Gene)
TGFB1I1Protein7041 (Entrez Gene)
RHOAProtein387 (Entrez Gene)
EFCAB6Protein64800 (Entrez Gene)
RHOBProtein388 (Entrez Gene)
BMFRna90427 (Entrez Gene)
ROCK1Protein6093 (Entrez Gene)
RNF14Protein9604 (Entrez Gene)
ROCK2Protein9475 (Entrez Gene)
AKT1Protein207 (Entrez Gene)
Actin polymerizationProtein
NCOA4Protein8031 (Entrez Gene)
LIMK2Protein3985 (Entrez Gene)
PTK2Protein5747 (Entrez Gene) DHT and testosterone induces phosphorylation of FAK in LNCaP cells.
DSTNProtein11034 (Entrez Gene)
UBE3AProtein7337 (Entrez Gene)
NCOR1Protein9611 (Entrez Gene)
FOXO1Protein2308 (Entrez Gene)
NCOR2Protein9612 (Entrez Gene)
PPAP2ARna8611 (Entrez Gene)
PSMC3IPProtein29893 (Entrez Gene)
ETV5Protein2119 (Entrez Gene)
MYST2Protein11143 (Entrez Gene)
NCOA1Protein8648 (Entrez Gene)
RAD9AProtein5883 (Entrez Gene)
FLNAProtein2316 (Entrez Gene)
PAK6Protein56924 (Entrez Gene)
CALRProtein811 (Entrez Gene)
PATZ1Protein23598 (Entrez Gene)
UBE2IProtein7329 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
FHL2Protein2274 (Entrez Gene)
SMAD4Protein4089 (Entrez Gene)
NCOA2Protein10499 (Entrez Gene)
NCOA3Protein8202 (Entrez Gene)
CCNE1Protein898 (Entrez Gene)
TGIF1Protein
FKBP4Protein2288 (Entrez Gene)
NR2C2Protein7182 (Entrez Gene)
SIRT1Protein23411 (Entrez Gene)
PIAS1Protein8554 (Entrez Gene)
PARK7Protein11315 (Entrez Gene)
SMAD3Protein4088 (Entrez Gene)
CARM1Protein10498 (Entrez Gene)
AESProtein166 (Entrez Gene)
KAT2BProtein8850 (Entrez Gene)
PIAS3Protein10401 (Entrez Gene)
RNF6Protein6049 (Entrez Gene)
STAT3Protein6774 (Entrez Gene)
RLN1GeneProduct6013 (Entrez Gene)
SP1Protein6667 (Entrez Gene)
SIN3AProtein25942 (Entrez Gene)
CDKN1ARna1026 (Entrez Gene)
NR0B2Protein8431 (Entrez Gene)
HDAC1Protein3065 (Entrez Gene)
SRCProtein6714 (Entrez Gene)
MDM2Protein4193 (Entrez Gene)
RANProtein5901 (Entrez Gene)
BAG1Protein573 (Entrez Gene)
PIAS4Protein51588 (Entrez Gene)
STUB1Protein10273 (Entrez Gene)
EP300Protein2033 (Entrez Gene)
RUNX2Protein860 (Entrez Gene)
GNB2L1Protein10399 (Entrez Gene)
RB1Protein5925 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
DAXXProtein1616 (Entrez Gene)
PTENProtein5728 (Entrez Gene)
EGFRProtein1956 (Entrez Gene)
PIAS2Protein9063 (Entrez Gene)
PRDX1Protein5052 (Entrez Gene)
CCND1Protein595 (Entrez Gene)
ZMIZ1Protein57178 (Entrez Gene)
CREBBPProtein1387 (Entrez Gene)
SUMO1Protein7341 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
SMARCE1Protein6605 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
KDM1AProtein23028 (Entrez Gene)
KAT5Protein10524 (Entrez Gene)
TZFProtein24149 (Entrez Gene)
RNF4Protein6047 (Entrez Gene)
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