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

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none cytosolnucleoplasmAR:Androgenp-T774-PKN1p-T774-PKN1:AR:Androgenp-T774-PKN1:AR:AndrogenNCOA2p-T774-PKN1:AR:Androgen:NCOA2KLK2,3Gene:Nucleosomewith Me3K-10-H3p-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with Me3K-10-H3ATPp-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12,Me3K-10-H3ADPp-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12, Me3K-10-H3:KDM4CKDM4CO22OGp-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-Me2K-10-H3CH2OCO2SUCCAKDM1Ap-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,Me2K-10-H3:KDM1Ap-T774-PKN1:AR:Androgen:KLK2,KLK3 Gene:Nucleosome with p-T12,MeK-10-H3:KDM1A2OGO2CO2SUCCACH2Op-T774-PKN1:AR:Androgen:KLK2,3 Gene:Nucleosome with p-T12-H32OGO2CO2SUCCACH2OKLK2,3 genesKLK2,KLK3RHO GTPases activatePKNsDHTESTTEST6-Dehydrotestosteroneandrost-4-en-3,17-dioneARp-T774-PKN1DHTESTTEST6-Dehydrotestosteroneandrost-4-en-3,17-dioneARp-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-Dehydrotestosteronep-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneNCOA2KLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSMe3K-10-HIST1H3AMe3K-10-HIST2H3AMe3K-10-H3F3Ap-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneKLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSMe3K-10-HIST1H3AMe3K-10-HIST2H3AMe3K-10-H3F3Ap-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneKLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSp-T12, Me3K-10-HIST1H3Ap-T12, Me3K-10-HIST2H3Ap-T12,Me3K-10-H3F3Ap-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneKLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSp-T12, Me3K-10-HIST1H3Ap-T12, Me3K-10-HIST2H3Ap-T12,Me3K-10-H3F3AKDM4Cp-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneKLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSp-T12, Me2K-10-H3F3Ap-T12, Me2K-10-HIST1H3Ap-T12, Me2K-10-HIST2H3AKDM1Ap-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneKLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSp-T12, Me2K-10-H3F3Ap-T12, Me2K-10-HIST1H3Ap-T12, Me2K-10-HIST2H3AKDM1Ap-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneKLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSp-T12,MeK-10-HIST1H3Ap-T12,MeK-H3F3Ap-T12,MeK-HIST2H3Ap-T774-PKN1ARDHTESTTESTandrost-4-en-3,17-dione6-DehydrotestosteroneKLK2 GeneKLK3 GeneHIST1H4H2AFB1HIST1H2ABHIST1H2AJHIST1H2ADHIST1H2ACHIST2H2AA3HIST2H2ACH2AFJH2AFVH2AFXH2AFZHIST1H2BKHIST3H2BBHIST1H2BAHIST1H2BCHIST1H2BDHIST1H2BLHIST1H2BNHIST1H2BMHIST1H2BBHIST1H2BHHIST1H2BOHIST2H2BEHIST1H2BJH2BFSp-T12-H3F3Ap-T12-HIST1H3Ap-T12-HIST2H3AKLK2 GeneKLK3 GeneKLK2KLK3Name: Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3Organism: Homo sapiens


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: 61
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. 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
  2. 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
  3. 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
  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
  5. Kato T, Gotoh Y, Hoffmann A, Ono Y.; ''Negative regulation of constitutive NF-kappaB and JNK signaling by PKN1-mediated phosphorylation of TRAF1.''; PubMed
  6. Hutchinson CL, Lowe PN, McLaughlin SH, Mott HR, Owen D.; ''Mutational analysis reveals a single binding interface between RhoA and its effector, PRK1.''; PubMed
  7. 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
  8. 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
  9. 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
  10. 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
  11. Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y.; ''Interaction of PKN with alpha-actinin.''; PubMed
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  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
  20. 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
  21. 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

History

View all...
CompareRevisionActionTimeUserComment
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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