Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (Homo sapiens)

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6, 11, 1411, 146668, 14141414148, 1411, 14nucleoplasmcytosolHIST1H2AB HIST1H2BK p-T12, Me3K-10-HIST2H3A HIST1H2BB HIST1H2AJ H2BFS HIST1H2BL HIST1H2BD HIST1H2BK HIST2H2BE 2OGHIST1H2BM Me3K-10-H3F3A H2AFZ HIST1H2BD HIST1H2BN HIST1H2BJ HIST1H2BD HIST1H2BN p-T12,Me3K-10-H3F3A HIST1H2BK 6-Dehydrotestosterone HIST1H2AC KDM1A HIST1H2BC KLK2 Gene HIST1H2BK H2AFV HIST3H2BB HIST2H2BE HIST2H2BE CH2ODHTEST HIST1H2BO H2AFZ TEST HIST1H2AJ HIST1H2BC androst-4-en-3,17-dione HIST1H2BC H2BFS HIST1H2BJ HIST1H2AB H2AFV 6-Dehydrotestosterone HIST1H2AC p-T12, Me2K-10-HIST1H3A HIST1H2BN androst-4-en-3,17-dione HIST1H2BC HIST1H2BC HIST1H2BA HIST1H2AB HIST1H2BA HIST1H2BA KDM1A HIST1H2BM HIST1H2BM KLK2 H2AFB1 KDM1AH2BFS p-T12,MeK-10-HIST1H3A H2AFB1 KLK3 Gene p-T774-PKN1 HIST1H2BO TEST HIST2H2AC HIST1H2BO HIST2H2AA3 H2AFX TEST p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12,Me3K-10-H3HIST1H2BM HIST1H2BH HIST1H2BB AR:AndrogenHIST1H2BC HIST1H2AJ p-T12, Me2K-10-HIST1H3A HIST1H2BB p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12, Me3K-10-H3:KDM4Candrost-4-en-3,17-dione HIST2H2AA3 AR H2AFB1 KLK2 Gene HIST1H2AJ HIST3H2BB KLK3 Gene HIST1H2BO HIST1H2BO H2AFV HIST1H2AB RHO GTPases activatePKNsHIST1H2AD HIST1H4 HIST1H2BK 2OG6-Dehydrotestosterone HIST1H4 H2BFS TEST DHTEST TEST HIST2H2AC HIST1H2AD CH2OHIST1H2BB androst-4-en-3,17-dione p-T12-H3F3A androst-4-en-3,17-dione H2AFJ HIST1H2BA H2AFJ AR HIST1H2BO HIST1H2AD CH2ODHTEST H2AFJ AR HIST1H2AD HIST2H2AC KLK2 Gene KLK2 Gene KLK2 Gene HIST1H2BN DHTEST 6-Dehydrotestosterone ATPKLK3 Gene androst-4-en-3,17-dione TEST ADPp-T774-PKN1 KLK2,3Gene:Nucleosomewith Me3K-10-H3p-T774-PKN1 AR Me3K-10-HIST2H3A HIST1H2BA KLK3 H2AFJ p-T12-HIST2H3A 6-Dehydrotestosterone HIST1H2BN H2BFS HIST2H2AA3 HIST1H2BD androst-4-en-3,17-dione HIST3H2BB TEST HIST1H2AC HIST1H2BO HIST1H2AJ p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with Me3K-10-H3HIST1H2BL DHTEST androst-4-en-3,17-dione CO2H2AFJ HIST1H2BK 6-Dehydrotestosterone HIST1H2BL HIST1H2AJ TEST KLK3 Gene HIST2H2AC p-T12,Me3K-10-H3F3A HIST1H2AJ H2AFB1 HIST2H2AA3 HIST3H2BB HIST2H2AC HIST1H2BH H2AFJ DHTEST 6-Dehydrotestosterone H2BFS AR CO2p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-Me2K-10-H3Me3K-10-HIST2H3A SUCCAHIST3H2BB HIST1H2BM HIST1H2AC HIST1H2BL HIST1H2BJ HIST1H2BM p-T12, Me2K-10-H3F3A H2AFX HIST1H2BA HIST1H2BC HIST1H4 HIST1H2BD HIST2H2AC HIST1H2BN SUCCANCOA2 KLK3 Gene HIST1H2BB HIST1H2BB KLK2 Gene HIST1H2AB HIST1H2AC H2AFZ p-T774-PKN1 H2AFB1 DHTEST H2BFS p-T774-PKN1 p-T774-PKN1 HIST1H2BL Me3K-10-HIST1H3A p-T774-PKN1:AR:Androgenp-T12, Me2K-10-HIST2H3A HIST1H2BO KLK3 Gene 2OGHIST1H2BH HIST1H2AB HIST1H2BH HIST2H2AC HIST1H4 HIST1H2BJ HIST2H2AA3 6-Dehydrotestosterone androst-4-en-3,17-dione HIST2H2AA3 HIST1H2AC HIST1H2AC HIST1H2BL HIST1H4 HIST2H2AA3 p-T774-PKN1 H2AFV H2AFB1 H2AFZ HIST1H2BB HIST1H2BA HIST1H2AJ HIST1H2BH androst-4-en-3,17-dione HIST2H2BE KLK2 Gene KLK2 Gene HIST1H2BH AR KLK3 Gene HIST1H2BJ p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,MeK-10-H3:KDM1AHIST1H2BD HIST1H2BM HIST1H2AB KLK2,KLK3HIST2H2BE H2AFV HIST2H2BE O2KLK3 Gene HIST1H2BC p-T12, Me2K-10-HIST2H3A H2AFV H2AFX KLK3 Gene HIST1H2AD KLK2,3 genesAR TEST p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,Me2K-10-H3:KDM1AH2AFX AR p-T774-PKN1 HIST1H2AD H2AFV HIST1H4 HIST1H2BN HIST3H2BB HIST1H2BH HIST3H2BB H2AFV TEST HIST1H2BB HIST1H2BJ HIST1H4 p-T774-PKN1:AR:AndrogenAR H2AFB1 AR O26-Dehydrotestosterone HIST2H2BE HIST1H2AB O2AR p-T12, Me3K-10-HIST2H3A H2BFS HIST1H4 p-T774-PKN1 H2AFX p-T12-HIST1H3A Me3K-10-H3F3A p-T774-PKN1 CO2HIST1H2BN p-T12,MeK-H3F3A H2AFJ HIST1H2BD HIST2H2BE DHTEST p-T12, Me3K-10-HIST1H3A HIST1H2BJ androst-4-en-3,17-dione H2AFX SUCCAHIST1H2BA H2AFZ DHTEST Me3K-10-HIST1H3A H2AFZ HIST2H2AC H2AFB1 NCOA2p-T774-PKN1:AR:Androgen:NCOA2HIST1H2AC H2AFX HIST1H2BK HIST1H2AD HIST1H2BJ HIST1H2BK HIST1H2BD HIST1H2BH 6-Dehydrotestosterone HIST1H2BL HIST2H2AA3 p-T12,MeK-HIST2H3A 6-Dehydrotestosterone HIST1H2BM p-T12, Me2K-10-H3F3A H2AFX DHTEST H2AFZ DHTEST p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-H3HIST1H2BL KDM4C H2AFJ HIST3H2BB H2AFZ KLK2 Gene KDM4CHIST1H2AD p-T774-PKN1p-T12, Me3K-10-HIST1H3A TEST 141414146146614141-5, 7, 9...


Description

PKN1, activated by phosphorylation at threonine T774, binds activated AR (androgen receptor) and promotes transcription from AR-regulated promoters. On one hand, phosphorylated PKN1 promotes the formation of a functional complex of AR with the transcriptional coactivator NCOA2 (TIF2) (Metzger et al. 2003). On the other hand, binding of phosphorylated PKN1, in complex with the activated AR, to androgen-reponsive promoters of KLK2 and KLK3 (PSA) genes, leads to PKN1-mediated histone phosphorylation. PKN1-phosphorylated histones recruit histone demethylases KDM4C (JMJD2C) and KDM1A (LSD1), and the ensuing demethylation of histones associated with the promoter regions of KLK2 and KLK3 genes increases their transcription (Metzger et al. 2005, Metzger et al. 2008). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 5625886
Reactome-version 
Reactome version: 64
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

Quality Tags

Ontology Terms

 

Bibliography

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  1. Metzger E, Wissmann M, Yin N, Müller JM, Schneider R, Peters AH, Günther T, Buettner R, Schüle R.; ''LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription.''; PubMed Europe PMC Scholia
  2. Modha R, Campbell LJ, Nietlispach D, Buhecha HR, Owen D, Mott HR.; ''The Rac1 polybasic region is required for interaction with its effector PRK1.''; PubMed Europe PMC Scholia
  3. Owen D, Lowe PN, Nietlispach D, Brosnan CE, Chirgadze DY, Parker PJ, Blundell TL, Mott HR.; ''Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1).''; PubMed Europe PMC Scholia
  4. Torbett NE, Casamassima A, Parker PJ.; ''Hyperosmotic-induced protein kinase N 1 activation in a vesicular compartment is dependent upon Rac1 and 3-phosphoinositide-dependent kinase 1.''; PubMed Europe PMC Scholia
  5. Matsuzawa K, Kosako H, Inagaki N, Shibata H, Mukai H, Ono Y, Amano M, Kaibuchi K, Matsuura Y, Azuma I, Inagaki M.; ''Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN.''; PubMed Europe PMC Scholia
  6. Metzger E, Müller JM, Ferrari S, Buettner R, Schüle R.; ''A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer.''; PubMed Europe PMC Scholia
  7. Hamaguchi T, Ito M, Feng J, Seko T, Koyama M, Machida H, Takase K, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T.; ''Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N.''; PubMed Europe PMC Scholia
  8. Metzger E, Yin N, Wissmann M, Kunowska N, Fischer K, Friedrichs N, Patnaik D, Higgins JM, Potier N, Scheidtmann KH, Buettner R, Schüle R.; ''Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation.''; PubMed Europe PMC Scholia
  9. Maesaki R, Ihara K, Shimizu T, Kuroda S, Kaibuchi K, Hakoshima T.; ''The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1.''; PubMed Europe PMC Scholia
  10. Palmer RH, Dekker LV, Woscholski R, Le Good JA, Gigg R, Parker PJ.; ''Activation of PRK1 by phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. A comparison with protein kinase C isotypes.''; PubMed Europe PMC Scholia
  11. Misaki K, Mukai H, Yoshinaga C, Oishi K, Isagawa T, Takahashi M, Ohsumi K, Kishimoto T, Ono Y.; ''PKN delays mitotic timing by inhibition of Cdc25C: possible involvement of PKN in the regulation of cell division.''; PubMed Europe PMC Scholia
  12. Kato T, Gotoh Y, Hoffmann A, Ono Y.; ''Negative regulation of constitutive NF-kappaB and JNK signaling by PKN1-mediated phosphorylation of TRAF1.''; PubMed Europe PMC Scholia
  13. Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y.; ''Interaction of PKN with alpha-actinin.''; PubMed Europe PMC Scholia
  14. Flynn P, Mellor H, Casamassima A, Parker PJ.; ''Rho GTPase control of protein kinase C-related protein kinase activation by 3-phosphoinositide-dependent protein kinase.''; PubMed Europe PMC Scholia
  15. Yoshinaga C, Mukai H, Toshimori M, Miyamoto M, Ono Y.; ''Mutational analysis of the regulatory mechanism of PKN: the regulatory region of PKN contains an arachidonic acid-sensitive autoinhibitory domain.''; PubMed Europe PMC Scholia
  16. Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y.; ''Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases.''; PubMed Europe PMC Scholia
  17. Hutchinson CL, Lowe PN, McLaughlin SH, Mott HR, Owen D.; ''Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB.''; PubMed Europe PMC Scholia
  18. Dettori R, Sonzogni S, Meyer L, Lopez-Garcia LA, Morrice NA, Zeuzem S, Engel M, Piiper A, Neimanis S, Frödin M, Biondi RM.; ''Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1).''; PubMed Europe PMC Scholia
  19. Collazos A, Michael N, Whelan RD, Kelly G, Mellor H, Pang LC, Totty N, Parker PJ.; ''Site recognition and substrate screens for PKN family proteins.''; PubMed Europe PMC Scholia
  20. Hutchinson CL, Lowe PN, McLaughlin SH, Mott HR, Owen D.; ''Mutational analysis reveals a single binding interface between RhoA and its effector, PRK1.''; PubMed Europe PMC Scholia
  21. Zong H, Raman N, Mickelson-Young LA, Atkinson SJ, Quilliam LA.; ''Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
113060view10:58, 2 November 2020ReactomeTeamReactome version 74
112293view15:12, 9 October 2020ReactomeTeamReactome version 73
101273view11:16, 1 November 2018ReactomeTeamreactome version 66
100811view20:46, 31 October 2018ReactomeTeamreactome version 65
100352view19:22, 31 October 2018ReactomeTeamreactome version 64
99897view16:04, 31 October 2018ReactomeTeamreactome version 63
99454view14:38, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99118view12:40, 31 October 2018ReactomeTeamreactome version 62
93760view13:34, 16 August 2017ReactomeTeamreactome version 61
93282view11:19, 9 August 2017ReactomeTeamreactome version 61
87075view14:20, 18 July 2016MkutmonOntology Term : 'signaling pathway' added !
86362view09:16, 11 July 2016ReactomeTeamreactome version 56
83473view13:25, 18 November 2015ReactomeTeamVersion54
81597view13:08, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2OGMetaboliteCHEBI:30915 (ChEBI)
6-Dehydrotestosterone MetaboliteCHEBI:29117 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
AR ProteinP10275 (Uniprot-TrEMBL)
AR:AndrogenComplexR-HSA-5625732 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
CH2OMetaboliteCHEBI:16842 (ChEBI)
CO2MetaboliteCHEBI:16526 (ChEBI)
DHTEST MetaboliteCHEBI:16330 (ChEBI)
H2AFB1 ProteinP0C5Y9 (Uniprot-TrEMBL)
H2AFJ ProteinQ9BTM1 (Uniprot-TrEMBL)
H2AFV ProteinQ71UI9 (Uniprot-TrEMBL)
H2AFX ProteinP16104 (Uniprot-TrEMBL)
H2AFZ ProteinP0C0S5 (Uniprot-TrEMBL)
H2BFS ProteinP57053 (Uniprot-TrEMBL)
HIST1H2AB ProteinP04908 (Uniprot-TrEMBL)
HIST1H2AC ProteinQ93077 (Uniprot-TrEMBL)
HIST1H2AD ProteinP20671 (Uniprot-TrEMBL)
HIST1H2AJ ProteinQ99878 (Uniprot-TrEMBL)
HIST1H2BA ProteinQ96A08 (Uniprot-TrEMBL)
HIST1H2BB ProteinP33778 (Uniprot-TrEMBL)
HIST1H2BC ProteinP62807 (Uniprot-TrEMBL)
HIST1H2BD ProteinP58876 (Uniprot-TrEMBL)
HIST1H2BH ProteinQ93079 (Uniprot-TrEMBL)
HIST1H2BJ ProteinP06899 (Uniprot-TrEMBL)
HIST1H2BK ProteinO60814 (Uniprot-TrEMBL)
HIST1H2BL ProteinQ99880 (Uniprot-TrEMBL)
HIST1H2BM ProteinQ99879 (Uniprot-TrEMBL)
HIST1H2BN ProteinQ99877 (Uniprot-TrEMBL)
HIST1H2BO ProteinP23527 (Uniprot-TrEMBL)
HIST1H4 ProteinP62805 (Uniprot-TrEMBL)
HIST2H2AA3 ProteinQ6FI13 (Uniprot-TrEMBL)
HIST2H2AC ProteinQ16777 (Uniprot-TrEMBL)
HIST2H2BE ProteinQ16778 (Uniprot-TrEMBL)
HIST3H2BB ProteinQ8N257 (Uniprot-TrEMBL)
KDM1A ProteinO60341 (Uniprot-TrEMBL)
KDM1AProteinO60341 (Uniprot-TrEMBL)
KDM4C ProteinQ9H3R0 (Uniprot-TrEMBL)
KDM4CProteinQ9H3R0 (Uniprot-TrEMBL)
KLK2 Gene ProteinENSG00000167751 (Ensembl)
KLK2 ProteinP20151 (Uniprot-TrEMBL)
KLK2,3

Gene:Nucleosome

with Me3K-10-H3
ComplexR-HSA-5625764 (Reactome)
KLK2,3 genesComplexR-HSA-5625769 (Reactome)
KLK2,KLK3ComplexR-HSA-5625882 (Reactome)
KLK3 Gene ProteinENSG00000142515 (Ensembl)
KLK3 ProteinP07288 (Uniprot-TrEMBL)
Me3K-10-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me3K-10-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
Me3K-10-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
NCOA2 ProteinQ15596 (Uniprot-TrEMBL)
NCOA2ProteinQ15596 (Uniprot-TrEMBL)
O2MetaboliteCHEBI:15379 (ChEBI)
RHO GTPases activate PKNsPathwayR-HSA-5625740 (Reactome) Protein kinases N (PKN), also known as protein kinase C-related kinases (PKR) feature a C-terminal serine/threonine kinase domain and three RHO-binding motifs at the N-terminus. RHO GTPases RHOA, RHOB, RHOC and RAC1 bind PKN1, PKN2 and PKN3 (Maesaki et al. 1999, Zhong et al. 1999, Owen et al. 2003, Modha et al. 2008, Hutchinson et al. 2011, Hutchinson et al. 2013), bringing them in proximity to the PIP3-activated co-activator PDPK1 (PDK1) (Flynn et al. 2000, Torbett et al. 2003). PDPK1 phosphorylates PKNs on a highly conserved threonine residue in the kinase activation loop, which is a prerequisite for PKN activation. Phosphorylation of other residues might also be involved in activation (Flynn et al. 2000, Torbett et al. 2003, Dettori et al. 2009). PKNs are activated by fatty acids like arachidonic acid and phospholipids in vitro, but the in vivo significance of this activation remains unclear (Palmer et al. 1995, Yoshinaga et al. 1999).

PKNs play important roles in diverse functions, including regulation of cell cycle, receptor trafficking, vesicle transport and apoptosis. PKN is also involved in the ligand-dependent transcriptional activation by the androgen receptor. More than 20 proteins and several peptides have been shown to be phosphorylated by PKN1 and PKN2, including CPI-17 (Hamaguchi et al. 2000), alpha-actinin (Mukai et al. 1997), adducin (Collazos et al. 2011), CDC25C (Misaki et al. 2001), vimentin (Matsuzawa et al. 1997), TRAF1 (Kato et al. 2008), CLIP170 (Collazos et al. 2011) and EGFR (Collazos et al. 2011). There are no known substrates for PKN3 (Collazos et al. 2011).

SUCCAMetaboliteCHEBI:15741 (ChEBI)
TEST MetaboliteCHEBI:17347 (ChEBI)
androst-4-en-3,17-dione MetaboliteCHEBI:16422 (ChEBI)
p-T12, Me2K-10-H3F3A ProteinP84243 (Uniprot-TrEMBL)
p-T12, Me2K-10-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
p-T12, Me2K-10-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
p-T12, Me3K-10-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
p-T12, Me3K-10-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
p-T12,Me3K-10-H3F3A ProteinP84243 (Uniprot-TrEMBL)
p-T12,MeK-10-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
p-T12,MeK-H3F3A ProteinP84243 (Uniprot-TrEMBL)
p-T12,MeK-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
p-T12-H3F3A ProteinP84243 (Uniprot-TrEMBL)
p-T12-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
p-T12-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
p-T774-PKN1 ProteinQ16512 (Uniprot-TrEMBL)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with Me3K-10-H3ComplexR-HSA-5625776 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12, Me3K-10-H3:KDM4CComplexR-HSA-5625795 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12,Me3K-10-H3ComplexR-HSA-5625782 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-H3ComplexR-HSA-5625874 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-Me2K-10-H3ComplexR-HSA-5625789 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,Me2K-10-H3:KDM1AComplexR-HSA-5625850 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,MeK-10-H3:KDM1AComplexR-HSA-5625863 (Reactome)
p-T774-PKN1:AR:Androgen:NCOA2ComplexR-HSA-5625718 (Reactome)
p-T774-PKN1:AR:AndrogenComplexR-HSA-5625734 (Reactome)
p-T774-PKN1:AR:AndrogenComplexR-HSA-5625736 (Reactome)
p-T774-PKN1ProteinQ16512 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
2OGR-HSA-5625797 (Reactome)
2OGR-HSA-5625848 (Reactome)
2OGR-HSA-5625870 (Reactome)
ADPArrowR-HSA-5625784 (Reactome)
AR:AndrogenR-HSA-5625717 (Reactome)
ATPR-HSA-5625784 (Reactome)
CH2OArrowR-HSA-5625797 (Reactome)
CH2OArrowR-HSA-5625848 (Reactome)
CH2OArrowR-HSA-5625870 (Reactome)
CO2ArrowR-HSA-5625797 (Reactome)
CO2ArrowR-HSA-5625848 (Reactome)
CO2ArrowR-HSA-5625870 (Reactome)
KDM1AArrowR-HSA-5625870 (Reactome)
KDM1AR-HSA-5625849 (Reactome)
KDM4CArrowR-HSA-5625797 (Reactome)
KDM4CR-HSA-5625796 (Reactome)
KLK2,3

Gene:Nucleosome

with Me3K-10-H3
R-HSA-5625774 (Reactome)
KLK2,3 genesR-HSA-5625883 (Reactome)
KLK2,KLK3ArrowR-HSA-5625883 (Reactome)
NCOA2R-HSA-5625745 (Reactome)
O2R-HSA-5625797 (Reactome)
O2R-HSA-5625848 (Reactome)
O2R-HSA-5625870 (Reactome)
R-HSA-5625717 (Reactome) Activated PKN1 binds androgen-activated AR (androgen receptor) (Metzger et al. 2003).
R-HSA-5625738 (Reactome) Binding of activated PKN1 to the androgen-activated AR (androgen receptor) promotes translocation of the p-T774-PKN1:AR:Androgen complex into the nucleus (Metzger et al. 2003).
R-HSA-5625745 (Reactome) Binding of PKN1 to androgen-activated AR (androgen receptor) promotes the formation of a functional complex of AR with the transcriptional coactivator NCOA2 (TIF2) (Metzger et al. 2003).
R-HSA-5625774 (Reactome) PKN1 in complex with the activated AR (androgen receptor) binds promoters of KLK2 and KLK3 (PSA) genes (Metzger et al. 2008).
R-HSA-5625784 (Reactome) PKN1 (PRK1), recruited to promoters of KLK2 and KLK3 (PSA) genes through association with the activated androgen receptor (AR), phosphorylates promoter-bound nucleosomes on threonine residue T12 (also labeled as T11 in literature) of histone 3, creating the H3T11 mark (Metzger et al. 2008).
R-HSA-5625796 (Reactome) Phosphorylation of histone 3 at threonine residue T12 (also labeled in literature as T11) by PKN1 enables recruitment of demethylase KDM4C (JMJD2C) to trimethylated histone 3 at KLK2 and KLK3 promoters (Metzger et al. 2008). KDM4C specifically binds to trimethylated lysine residues (Whetstine et al. 2006).
R-HSA-5625797 (Reactome) KDM4C (JMJD2C) demethylates trimethylated lysine K10 of histone 3 in nucleosomes associated with promoters of KLK2 and KLK3 (PSA) genes (Metzger et al. 2008), converting it to dimethylated lysine (Whetstine et al. 2006).
R-HSA-5625848 (Reactome) PKN1-mediated phosphorylation of histone H3 threonine residue T12 (also labeled in literature as Thr11) enables demethylation of histone H3 lysine K10 (also labeled in literature as K9) by demethylase KDM1A (LSD1) (Metzger et al. 2008). KDM1A acts on dimethylated and monomethylated H3K9 at AR-regulated promoters (Metzger et al. 2005), so it is shown that demethylation of dimethylated H3K9 (Me2K-10-H3) by KDM1A happens after demethylation of trimethylated H3K9 (Me3K-10-H3) by KDM4C (JMJD2C).
R-HSA-5625849 (Reactome) PKN1-mediated phosphorylation of histone H3 threonine residue 12 (also labeled in literature as Thr11) enables recruitment of KDM1A (LSD1) demethylase to AR-regulated promoters KLK2 and KLK3 (PSA) (Metzger et al. 2008).
R-HSA-5625870 (Reactome) PKN1-mediated phosphorylation of histone H3 threonine residue T12 (also labeled in literature as Thr11) enables demethylation of histone H3 lysine K10 (also labeled in literature as K9) by demethylase KDM1A (LSD1) (Metzger et al. 2008). KDM1A acts on dimethylated and monomethylated H3K9 at AR-regulated promoters (Metzger et al. 2005), so it is shown that KDM1A-mediated demethylation of monomethylated H3K9 (MeK-10-H3) happens sequentially after KDM1A-mediated demethylation of dimethylated H3K9 (Me2K-10-H3).
R-HSA-5625883 (Reactome) PKN1-facilitated demethylation of histones at promoters of KLK2 and KLK3 genes stimulates transcription of KLK2 and KLK3 (Metzger et al. 2005, Metzger et al. 2008).
SUCCAArrowR-HSA-5625797 (Reactome)
SUCCAArrowR-HSA-5625848 (Reactome)
SUCCAArrowR-HSA-5625870 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with Me3K-10-H3ArrowR-HSA-5625774 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with Me3K-10-H3R-HSA-5625784 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with Me3K-10-H3mim-catalysisR-HSA-5625784 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12, Me3K-10-H3:KDM4CArrowR-HSA-5625796 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12, Me3K-10-H3:KDM4CR-HSA-5625797 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12, Me3K-10-H3:KDM4Cmim-catalysisR-HSA-5625797 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12,Me3K-10-H3ArrowR-HSA-5625784 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12,Me3K-10-H3R-HSA-5625796 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-H3ArrowR-HSA-5625870 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-H3ArrowR-HSA-5625883 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-Me2K-10-H3ArrowR-HSA-5625797 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-Me2K-10-H3R-HSA-5625849 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,Me2K-10-H3:KDM1AArrowR-HSA-5625849 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,Me2K-10-H3:KDM1AR-HSA-5625848 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,Me2K-10-H3:KDM1Amim-catalysisR-HSA-5625848 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,MeK-10-H3:KDM1AArrowR-HSA-5625848 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,MeK-10-H3:KDM1AR-HSA-5625870 (Reactome)
p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,MeK-10-H3:KDM1Amim-catalysisR-HSA-5625870 (Reactome)
p-T774-PKN1:AR:Androgen:NCOA2ArrowR-HSA-5625745 (Reactome)
p-T774-PKN1:AR:AndrogenArrowR-HSA-5625717 (Reactome)
p-T774-PKN1:AR:AndrogenArrowR-HSA-5625738 (Reactome)
p-T774-PKN1:AR:AndrogenR-HSA-5625738 (Reactome)
p-T774-PKN1:AR:AndrogenR-HSA-5625745 (Reactome)
p-T774-PKN1:AR:AndrogenR-HSA-5625774 (Reactome)
p-T774-PKN1R-HSA-5625717 (Reactome)
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