Protein kinase N1

PKN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1CXZ, 1URF, 2RMK, 4NKG, 4OTD, 4OTG, 4OTH, 4OTI
Identifiers
Aliases	PKN1 , DBK, PAK-1, PAK1, PKN, PKN-ALPHA, PRK1, PRKCL1, Protein kinase N1
External IDs	OMIM: 601032 MGI: 108022 HomoloGene: 48130 GeneCards: PKN1
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19p13.12 Start 14,433,053 bp [1] End 14,471,867 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8 C2|8 40.22 cM Start 84,393,165 bp [2] End 84,425,808 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lung stromal cell of endometrium ganglionic eminence monocyte upper lobe of left lung gastric mucosa spleen anterior pituitary right coronary artery left uterine tube Top expressed in thymus superior frontal gyrus external carotid artery right ventricle internal carotid artery yolk sac duodenum brown adipose tissue spleen proximal tubule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding protein kinase C activity histone binding histone deacetylase binding chromatin binding histone kinase activity (H3-T11 specific) kinase activity protein serine/threonine kinase activity protein binding androgen receptor binding nuclear receptor coactivator activity ATP binding protein kinase C binding Cellular component cytoplasm cytosol endosome membrane plasma membrane nucleoplasm midbody cleavage furrow nucleus cytoplasmic vesicle protein-containing complex Biological process regulation of germinal center formation negative regulation of protein phosphorylation renal system process regulation of transcription, DNA-templated B cell apoptotic process negative regulation of protein kinase activity phosphorylation regulation of transcription by RNA polymerase II B cell homeostasis spleen development hyperosmotic response transcription, DNA-templated regulation of cell motility protein phosphorylation peptidyl-serine phosphorylation epithelial cell migration negative regulation of B cell proliferation regulation of immunoglobulin production signal transduction chromatin organization positive regulation of nucleic acid-templated transcription intracellular signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5585 320795 Ensembl ENSG00000123143 ENSMUSG00000057672 UniProt Q16512 P70268 RefSeq (mRNA) NM_002741 NM_213560 NM_001199593 NM_177262 RefSeq (protein) NP_002732 NP_998725 NP_001186522 NP_796236 Location (UCSC) Chr 19: 14.43 – 14.47 Mb Chr 8: 84.39 – 84.43 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene. ^{[5] [6]}

Function

The protein encoded by this gene belongs to the protein kinase C superfamily. This kinase is activated by Rho family of small G proteins and may mediate the Rho-dependent signaling pathway. This kinase can be activated by phospholipids and by limited proteolysis. The 3-phosphoinositide dependent protein kinase-1 (PDPK1/PDK1) is reported to phosphorylate this kinase, which may mediate insulin signals to the actin cytoskeleton. The proteolytic activation of this kinase by caspase-3 or related proteases during apoptosis suggests its role in signal transduction related to apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been observed. ^[6]

Interactions

Protein kinase N1 has been shown to interact with:

• AKAP9, ^[7]
• Actinin, alpha 1, ^[8]
• CCDC85B, ^[9]
• NEFL, ^[10]
• NEUROD2 ^[11]
• Phosphoinositide-dependent kinase-1, ^[12]
• Phospholipase D1, ^[13]
• RHOA, ^{[14] [15] [16]} and
• Vimentin. ^[17]
• TRAF1. ^[18]

References

1. GRCh38: Ensembl release 89: ENSG00000123143 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057672 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bartsch JW, Mukai H, Takahashi N, Ronsiek M, Fuchs S, Jockusch H, Ono Y (June 1998). "The protein kinase N (PKN) gene PRKCL1/Prkcl1 maps to human chromosome 19p12-p13.1 and mouse chromosome 8 with close linkage to the myodystrophy (myd) mutation". Genomics. 49 (1): 129–32. doi:10.1006/geno.1997.5208. PMID   9570957.
6. "Entrez Gene: PKN1 protein kinase N1".
7. Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y (June 1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. 274 (24): 17267–74. doi: 10.1074/jbc.274.24.17267 . PMID   10358086.
8. Feng S, Reséndiz JC, Christodoulides N, Lu X, Arboleda D, Berndt MC, Kroll MH (January 2002). "Pathological shear stress stimulates the tyrosine phosphorylation of alpha-actinin associated with the glycoprotein Ib-IX complex". Biochemistry. 41 (4): 1100–8. doi:10.1021/bi0156005. PMID   11802708.
9. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
10. Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (April 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". J. Biol. Chem. 271 (16): 9816–22. doi: 10.1074/jbc.271.16.9816 . PMID   8621664.
11. Shibata H, Oda H, Mukai H, Oishi K, Misaki K, Ohkubo H, Ono Y (December 1999). "Interaction of PKN with a neuron-specific basic helix-loop-helix transcription factor, NDRF/NeuroD2". Brain Res. Mol. Brain Res. 74 (1–2): 126–34. doi:10.1016/s0169-328x(99)00273-9. PMID   10640683.
12. Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR (July 2000). "A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta (PKCzeta ) and PKC-related kinase 2 by PDK1". J. Biol. Chem. 275 (27): 20806–13. doi: 10.1074/jbc.M000421200 . PMID   10764742.
13. Oishi K, Takahashi M, Mukai H, Banno Y, Nakashima S, Kanaho Y, Nozawa Y, Ono Y (May 2001). "PKN regulates phospholipase D1 through direct interaction". J. Biol. Chem. 276 (21): 18096–101. doi: 10.1074/jbc.M010646200 . PMID   11259428.
14. Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003). "RhoE binds to ROCK I and inhibits downstream signaling". Mol. Cell. Biol. 23 (12): 4219–29. doi:10.1128/mcb.23.12.4219-4229.2003. PMC   156133 . PMID   12773565.
15. Alberts AS, Bouquin N, Johnston LH, Treisman R (April 1998). "Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the yeast response regulator protein Skn7". J. Biol. Chem. 273 (15): 8616–22. doi: 10.1074/jbc.273.15.8616 . PMID   9535835.
16. Flynn P, Mellor H, Palmer R, Panayotou G, Parker PJ (January 1998). "Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif". J. Biol. Chem. 273 (5): 2698–705. doi: 10.1074/jbc.273.5.2698 . PMID   9446575.
17. Matsuzawa K, Kosako H, Inagaki N, Shibata H, Mukai H, Ono Y, Amano M, Kaibuchi K, Matsuura Y, Azuma I, Inagaki M (May 1997). "Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN". Biochem. Biophys. Res. Commun. 234 (3): 621–5. doi:10.1006/bbrc.1997.6669. PMID   9175763.
18. Kato T, Gotoh Y, Hoffman A, Ono Y (May 2008). "Negative regulation of constitutive NF-kappaB and JNK signaling by PKN1-mediated phosphorylation of TRAF1". Genes Cells. 13 (5): 509–20. doi: 10.1111/j.1365-2443.2008.01182.x . PMID   18429822. S2CID   205292893.

Further reading

• Palmer RH, Ridden J, Parker PJ (1995). "Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family". Eur. J. Biochem. 227 (1–2): 344–51. doi: 10.1111/j.1432-1033.1995.tb20395.x . PMID   7851406.
• Chu W, Presky DH, Danho W, Swerlick RA, Burns DK (1994). "Identification and characterization of DBK, a novel putative serine/threonine protein kinase from human endothelial cells". Eur. J. Biochem. 225 (2): 695–702. doi: 10.1111/j.1432-1033.1994.00695.x . PMID   7957185.
• Palmer RH, Ridden J, Parker PJ (1994). "Identification of multiple, novel, protein kinase C-related gene products". FEBS Lett. 356 (1): 5–8. doi: 10.1016/0014-5793(94)01202-4 . PMID   7988719. S2CID   32020105.
• Mukai H, Ono Y (1994). "A novel protein kinase with leucine zipper-like sequences: its catalytic domain is highly homologous to that of protein kinase C". Biochem. Biophys. Res. Commun. 199 (2): 897–904. doi:10.1006/bbrc.1994.1313. PMID   8135837.
• Palmer RH, Schönwasser DC, Rahman D, Pappin DJ, Herget T, Parker PJ (1996). "PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163". FEBS Lett. 378 (3): 281–5. doi: 10.1016/0014-5793(95)01454-3 . PMID   8557118. S2CID   46417714.
• Amano M, Mukai H, Ono Y, Chihara K, Matsui T, Hamajima Y, Okawa K, Iwamatsu A, Kaibuchi K (1996). "Identification of a putative target for Rho as the serine-threonine kinase protein kinase N". Science. 271 (5249): 648–50. Bibcode:1996Sci...271..648A. doi:10.1126/science.271.5249.648. PMID   8571127. S2CID   206575961.
• Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". J. Biol. Chem. 271 (16): 9816–22. doi: 10.1074/jbc.271.16.9816 . PMID   8621664.
• Brown JL, Stowers L, Baer M, Trejo J, Coughlin S, Chant J (1996). "Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway". Curr. Biol. 6 (5): 598–605. Bibcode:1996CBio....6..598B. doi: 10.1016/S0960-9822(02)00546-8 . PMID   8805275. S2CID   9697114.
• Mukai H, Miyahara M, Sunakawa H, Shibata H, Toshimori M, Kitagawa M, Shimakawa M, Takanaga H, Ono Y (1996). "Translocation of PKN from the cytosol to the nucleus induced by stresses". Proc. Natl. Acad. Sci. U.S.A. 93 (19): 10195–9. Bibcode:1996PNAS...9310195M. doi: 10.1073/pnas.93.19.10195 . PMC   38360 . PMID   8816775.
• Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y (1997). "Interaction of PKN with alpha-actinin". J. Biol. Chem. 272 (8): 4740–6. doi: 10.1074/jbc.272.8.4740 . PMID   9030526.
• Matsuzawa K, Kosako H, Inagaki N, Shibata H, Mukai H, Ono Y, Amano M, Kaibuchi K, Matsuura Y, Azuma I, Inagaki M (1997). "Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN". Biochem. Biophys. Res. Commun. 234 (3): 621–5. doi:10.1006/bbrc.1997.6669. PMID   9175763.
• Goedert M, Hasegawa M, Jakes R, Lawler S, Cuenda A, Cohen P (1997). "Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases". FEBS Lett. 409 (1): 57–62. doi: 10.1016/S0014-5793(97)00483-3 . PMID   9199504. S2CID   36383041.
• Flynn P, Mellor H, Palmer R, Panayotou G, Parker PJ (1998). "Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif". J. Biol. Chem. 273 (5): 2698–705. doi: 10.1074/jbc.273.5.2698 . PMID   9446575.
• Bekri S, Adélaïde J, Merscher S, Grosgeorge J, Caroli-Bosc F, Perucca-Lostanlen D, Kelley PM, Pébusque MJ, Theillet C, Birnbaum D, Gaudray P (1997). "Detailed map of a region commonly amplified at 11q13-->q14 in human breast carcinoma". Cytogenet. Cell Genet. 79 (1–2): 125–31. doi:10.1159/000134699. PMID   9533029.
• Zheng-Fischhöfer Q, Biernat J, Mandelkow EM, Illenberger S, Godemann R, Mandelkow E (1998). "Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation". Eur. J. Biochem. 252 (3): 542–52. doi: 10.1046/j.1432-1327.1998.2520542.x . PMID   9546672.
• Takanaga H, Mukai H, Shibata H, Toshimori M, Ono Y (1998). "PKN interacts with a paraneoplastic cerebellar degeneration-associated antigen, which is a potential transcription factor". Exp. Cell Res. 241 (2): 363–72. doi:10.1006/excr.1998.4060. PMID   9637778.
• Takahashi M, Mukai H, Toshimori M, Miyamoto M, Ono Y (1998). "Proteolytic activation of PKN by caspase-3 or related protease during apoptosis". Proc. Natl. Acad. Sci. U.S.A. 95 (20): 11566–71. Bibcode:1998PNAS...9511566T. doi: 10.1073/pnas.95.20.11566 . PMC   21681 . PMID   9751706.
• Hanger DP, Betts JC, Loviny TL, Blackstock WP, Anderton BH (1998). "New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry". J. Neurochem. 71 (6): 2465–76. doi: 10.1046/j.1471-4159.1998.71062465.x . PMID   9832145. S2CID   45602824.
• Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y (1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. 274 (24): 17267–74. doi: 10.1074/jbc.274.24.17267 . PMID   10358086.