Protein kinase N1 explained

Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene.^{[1] [2]}

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.^[2]

Interactions

Protein kinase N1 has been shown to interact with:

• AKAP9,^[3]
• Actinin, alpha 1,^[4]
• CCDC85B,^[5]
• NEFL,^[6]
• NEUROD2^[7]
• Phosphoinositide-dependent kinase-1,^[8]
• Phospholipase D1,^[9]
• RHOA,^{[10] [11] [12]} and
• Vimentin.^[13]
• TRAF1.^[14]

Further reading

• Palmer RH, Ridden J, Parker PJ . Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family . Eur. J. Biochem. . 227 . 1–2 . 344–51 . 1995 . 7851406 . 10.1111/j.1432-1033.1995.tb20395.x . free .
• Chu W, Presky DH, Danho W, Swerlick RA, Burns DK . Identification and characterization of DBK, a novel putative serine/threonine protein kinase from human endothelial cells . Eur. J. Biochem. . 225 . 2 . 695–702 . 1994 . 7957185 . 10.1111/j.1432-1033.1994.00695.x . free .
• Palmer RH, Ridden J, Parker PJ . Identification of multiple, novel, protein kinase C-related gene products . FEBS Lett. . 356 . 1 . 5–8 . 1994 . 7988719 . 10.1016/0014-5793(94)01202-4 . 32020105 . free .
• Mukai H, Ono Y . 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 . 1994 . 8135837 . 10.1006/bbrc.1994.1313 .
• Palmer RH, Schönwasser DC, Rahman D, Pappin DJ, Herget T, Parker PJ . PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163 . FEBS Lett. . 378 . 3 . 281–5 . 1996 . 8557118 . 10.1016/0014-5793(95)01454-3 . 46417714 . free .
• Amano M, Mukai H, Ono Y, Chihara K, Matsui T, Hamajima Y, Okawa K, Iwamatsu A, Kaibuchi K . Identification of a putative target for Rho as the serine-threonine kinase protein kinase N . Science . 271 . 5249 . 648–50 . 1996 . 8571127 . 10.1126/science.271.5249.648 . 1996Sci...271..648A . 206575961 .
• Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y . PKN associates and phosphorylates the head-rod domain of neurofilament protein . J. Biol. Chem. . 271 . 16 . 9816–22 . 1996 . 8621664 . 10.1074/jbc.271.16.9816 . free .
• Brown JL, Stowers L, Baer M, Trejo J, Coughlin S, Chant J . Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway . Curr. Biol. . 6 . 5 . 598–605 . 1996 . 8805275 . 10.1016/S0960-9822(02)00546-8 . 9697114 . free . 1996CBio....6..598B .
• Mukai H, Miyahara M, Sunakawa H, Shibata H, Toshimori M, Kitagawa M, Shimakawa M, Takanaga H, Ono Y . Translocation of PKN from the cytosol to the nucleus induced by stresses . Proc. Natl. Acad. Sci. U.S.A. . 93 . 19 . 10195–9 . 1996 . 8816775 . 38360 . 10.1073/pnas.93.19.10195 . 1996PNAS...9310195M . free .
• Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y . Interaction of PKN with alpha-actinin . J. Biol. Chem. . 272 . 8 . 4740–6 . 1997 . 9030526 . 10.1074/jbc.272.8.4740 . free .
• 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 . Biochem. Biophys. Res. Commun. . 234 . 3 . 621–5 . 1997 . 9175763 . 10.1006/bbrc.1997.6669 .
• Goedert M, Hasegawa M, Jakes R, Lawler S, Cuenda A, Cohen P . Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases . FEBS Lett. . 409 . 1 . 57–62 . 1997 . 9199504 . 10.1016/S0014-5793(97)00483-3 . 36383041 . free .
• Flynn P, Mellor H, Palmer R, Panayotou G, Parker PJ . Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif . J. Biol. Chem. . 273 . 5 . 2698–705 . 1998 . 9446575 . 10.1074/jbc.273.5.2698 . free .
• Bekri S, Adélaïde J, Merscher S, Grosgeorge J, Caroli-Bosc F, Perucca-Lostanlen D, Kelley PM, Pébusque MJ, Theillet C, Birnbaum D, Gaudray P . Detailed map of a region commonly amplified at 11q13-->q14 in human breast carcinoma . Cytogenet. Cell Genet. . 79 . 1–2 . 125–31 . 1997 . 9533029 . 10.1159/000134699 .
• Zheng-Fischhöfer Q, Biernat J, Mandelkow EM, Illenberger S, Godemann R, Mandelkow E . 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 . 1998 . 9546672 . 10.1046/j.1432-1327.1998.2520542.x . free .
• Takanaga H, Mukai H, Shibata H, Toshimori M, Ono Y . PKN interacts with a paraneoplastic cerebellar degeneration-associated antigen, which is a potential transcription factor . Exp. Cell Res. . 241 . 2 . 363–72 . 1998 . 9637778 . 10.1006/excr.1998.4060 .
• Takahashi M, Mukai H, Toshimori M, Miyamoto M, Ono Y . Proteolytic activation of PKN by caspase-3 or related protease during apoptosis . Proc. Natl. Acad. Sci. U.S.A. . 95 . 20 . 11566–71 . 1998 . 9751706 . 21681 . 10.1073/pnas.95.20.11566 . 1998PNAS...9511566T . free .
• Hanger DP, Betts JC, Loviny TL, Blackstock WP, Anderton BH . 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 . 1998 . 9832145 . 10.1046/j.1471-4159.1998.71062465.x . 45602824 . free .
• Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y . 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 . 1999 . 10358086 . 10.1074/jbc.274.24.17267 . free .

Notes and References

1. Bartsch JW, Mukai H, Takahashi N, Ronsiek M, Fuchs S, Jockusch H, Ono Y . 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 . June 1998 . 9570957 . 10.1006/geno.1997.5208 .
2. Web site: Entrez Gene: PKN1 protein kinase N1.
3. Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y . 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 . June 1999 . 10358086 . 10.1074/jbc.274.24.17267. free .
4. Feng S, Reséndiz JC, Christodoulides N, Lu X, Arboleda D, Berndt MC, Kroll MH . Pathological shear stress stimulates the tyrosine phosphorylation of alpha-actinin associated with the glycoprotein Ib-IX complex . Biochemistry . 41 . 4 . 1100–8 . January 2002 . 11802708 . 10.1021/bi0156005.
5. 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
6. Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y . PKN associates and phosphorylates the head-rod domain of neurofilament protein . J. Biol. Chem. . 271 . 16 . 9816–22 . April 1996 . 8621664 . 10.1074/jbc.271.16.9816. free .
7. Shibata H, Oda H, Mukai H, Oishi K, Misaki K, Ohkubo H, Ono Y . 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 . December 1999 . 10640683 . 10.1016/s0169-328x(99)00273-9.
8. Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR . 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 . July 2000 . 10764742 . 10.1074/jbc.M000421200 . free .
9. Oishi K, Takahashi M, Mukai H, Banno Y, Nakashima S, Kanaho Y, Nozawa Y, Ono Y . PKN regulates phospholipase D1 through direct interaction . J. Biol. Chem. . 276 . 21 . 18096–101 . May 2001 . 11259428 . 10.1074/jbc.M010646200 . free .
10. Riento K, Guasch RM, Garg R, Jin B, Ridley AJ . RhoE binds to ROCK I and inhibits downstream signaling . Mol. Cell. Biol. . 23 . 12 . 4219–29 . June 2003 . 12773565 . 156133 . 10.1128/mcb.23.12.4219-4229.2003.
11. Alberts AS, Bouquin N, Johnston LH, Treisman R . 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 . April 1998 . 9535835 . 10.1074/jbc.273.15.8616. free .
12. Flynn P, Mellor H, Palmer R, Panayotou G, Parker PJ . Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif . J. Biol. Chem. . 273 . 5 . 2698–705 . January 1998 . 9446575 . 10.1074/jbc.273.5.2698. free .
13. 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 . Biochem. Biophys. Res. Commun. . 234 . 3 . 621–5 . May 1997 . 9175763 . 10.1006/bbrc.1997.6669 .
14. Kato T, Gotoh Y, Hoffman A, Ono Y . Negative regulation of constitutive NF-kappaB and JNK signaling by PKN1-mediated phosphorylation of TRAF1 . Genes Cells . 13 . 5 . 509–20 . May 2008 . 18429822 . 10.1111/j.1365-2443.2008.01182.x. 205292893 . free .