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

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2, 11, 2011, 202022016, 202211, 202016, 2020cytosolnucleoplasmHIST2H2BE H2AFB1 p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,MeK-10-H3:KDM1AHIST2H2AC KLK3 Gene H2AFZ H2AFJ p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-Me2K-10-H3HIST1H2BB 6-Dehydrotestosterone HIST2H2AC KLK3 Gene HIST1H2BO KLK2 Gene HIST2H2AC KLK2 Gene H2BFS HIST2H2BE TEST HIST1H2BC TEST HIST1H2AB p-T774-PKN1AR DHTEST H2AFX HIST1H2BM HIST1H2AC H2AFX H2AFB1 HIST1H2AB HIST1H2BJ 6-Dehydrotestosterone KDM1A HIST1H2BO CH2OHIST2H2AC DHTEST p-T12,Me3K-10-H3F3A HIST1H2BH DHTEST HIST1H2AD KLK3 Gene HIST1H2AD HIST2H2BE HIST1H2AC HIST1H2AD HIST2H2AC p-T12, Me2K-10-HIST1H3A H2AFV HIST1H2BO H2AFV HIST1H2BH TEST CO2HIST2H2AA3 Me3K-10-HIST1H3A DHTEST HIST1H2BJ H2AFJ androst-4-en-3,17-dione KLK3 Gene HIST1H2BC Me3K-10-H3F3A TEST HIST1H2AJ HIST1H4 HIST1H2AJ HIST1H2BK Me3K-10-HIST2H3A HIST1H2BH HIST1H2BC TEST TEST p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with Me3K-10-H3AR KLK2 Gene H2AFB1 SUCCAHIST2H2AA3 HIST1H2BO H2AFV H2AFZ HIST1H2BJ Me3K-10-HIST2H3A HIST2H2BE androst-4-en-3,17-dione HIST1H2BM HIST3H2BB androst-4-en-3,17-dione DHTEST HIST1H2BN HIST1H2BD HIST3H2BB HIST2H2AA3 HIST1H2AJ HIST2H2AA3 HIST1H2BD HIST3H2BB Me3K-10-H3F3A androst-4-en-3,17-dione H2AFJ HIST1H2BN p-T12, Me2K-10-HIST1H3A H2AFX p-T774-PKN1 H2AFJ HIST1H2BB androst-4-en-3,17-dione 6-Dehydrotestosterone HIST1H2BB HIST1H2AD p-T12, Me3K-10-HIST1H3A DHTEST ATPHIST1H2AD H2BFS HIST1H2AD p-T774-PKN1 HIST3H2BB CH2OHIST3H2BB p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12, Me3K-10-H3:KDM4Cp-T12, Me2K-10-HIST2H3A KDM4Cp-T774-PKN1:AR:AndrogenHIST1H2BH KLK3 Gene KLK2 Gene 6-Dehydrotestosterone HIST1H2BN DHTEST androst-4-en-3,17-dione HIST1H2BL 6-Dehydrotestosterone H2AFB1 HIST1H2BA p-T12,Me3K-10-H3F3A HIST1H2AB AR androst-4-en-3,17-dione HIST1H2BD HIST1H2BJ HIST1H2AB HIST1H2BK H2AFJ HIST2H2AC KLK3 Gene HIST1H2BC HIST2H2AC NCOA2HIST1H4 KDM1AO2HIST1H2BM CO2HIST1H2AC HIST1H2BJ H2AFJ 6-Dehydrotestosterone HIST1H2AJ H2BFS 2OGHIST1H2AB HIST1H4 HIST1H2AB p-T774-PKN1 HIST1H2AC KLK2 6-Dehydrotestosterone TEST KLK2 Gene HIST1H2BC HIST1H2BH HIST1H4 HIST1H2AJ H2AFX HIST1H2BC HIST1H2BJ HIST1H2AC H2AFZ AR H2BFS KLK2 Gene H2AFV SUCCAH2BFS CO2p-T774-PKN1 HIST1H2BN HIST1H2BJ RHO GTPases activatePKNsHIST1H2BD H2AFZ HIST1H4 p-T12-H3F3A p-T12-HIST2H3A HIST1H2BA HIST1H4 HIST1H4 H2AFJ HIST1H2BA HIST1H2BB p-T12, Me2K-10-HIST2H3A p-T774-PKN1 p-T774-PKN1 6-Dehydrotestosterone p-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,Me2K-10-H3:KDM1AHIST2H2AA3 DHTEST p-T12,MeK-HIST2H3A HIST1H2AB H2AFB1 O2p-T774-PKN1 p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-H3H2AFB1 H2AFJ p-T12, Me3K-10-HIST2H3A HIST1H2AJ TEST p-T774-PKN1 HIST1H2BH HIST1H2BK HIST1H2BO HIST1H2BO p-T12, Me2K-10-H3F3A HIST1H2BH H2AFB1 p-T774-PKN1 HIST1H4 HIST1H2BN HIST1H2BA H2AFZ ADPTEST HIST1H2BM HIST1H2BB HIST2H2AA3 KLK2,3 genesHIST1H2BL DHTEST HIST1H2BB androst-4-en-3,17-dione HIST1H2BL H2AFX p-T12-HIST1H3A SUCCAHIST1H2BD HIST1H2BK HIST2H2BE androst-4-en-3,17-dione H2AFB1 HIST1H2BK H2BFS HIST3H2BB KLK2,KLK3p-T12,MeK-H3F3A HIST2H2AA3 2OGHIST1H2AB KDM4C KLK2 Gene TEST AR KLK3 Gene HIST1H2BA AR p-T774-PKN1 AR HIST1H2BH KLK2 Gene CH2Oandrost-4-en-3,17-dione p-T774-PKN1:AR:Androgenp-T774-PKN1:AR:Androgen:NCOA2HIST1H2BN 6-Dehydrotestosterone HIST1H2BL 6-Dehydrotestosterone p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12,Me3K-10-H3AR:AndrogenKLK3 HIST1H2AC HIST1H2BO KLK2 Gene H2AFV HIST1H2AC HIST1H2BC H2AFV KLK3 Gene androst-4-en-3,17-dione 2OGHIST1H2BM p-T12,MeK-10-HIST1H3A HIST1H2BA O2HIST1H2BD HIST1H2BB HIST1H2AJ HIST1H2BK HIST1H2BA p-T12, Me2K-10-H3F3A HIST1H2BL HIST1H2BK H2AFV KDM1A HIST1H2BN AR 6-Dehydrotestosterone H2AFX HIST2H2BE HIST1H2BB HIST2H2AC H2AFZ HIST1H2BA KLK2,3Gene:Nucleosomewith Me3K-10-H3H2AFZ AR HIST1H2BM HIST1H2BD KLK3 Gene HIST1H2BC HIST2H2BE HIST1H2AD HIST2H2AA3 HIST3H2BB AR H2BFS HIST1H2BO HIST1H2BM HIST1H2BK NCOA2 HIST1H2BD HIST2H2BE HIST1H2BL HIST1H2AC HIST1H2BN p-T12, Me3K-10-HIST1H3A AR HIST1H2BL H2AFX H2BFS TEST H2AFX H2AFZ HIST1H2BJ HIST1H2BM HIST1H2AD HIST1H2BL HIST1H2AJ DHTEST p-T12, Me3K-10-HIST2H3A HIST3H2BB H2AFV DHTEST Me3K-10-HIST1H3A 2201, 3-10, 12...20202022022020


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: 62
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

Quality Tags

Ontology Terms

 

Bibliography

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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  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. 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
  13. 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
  14. 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
  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. 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
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History

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CompareRevisionActionTimeUserComment
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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