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Gene Review

PKN1  -  protein kinase N1

Homo sapiens

Synonyms: DBK, MGC46204, PAK-1, PAK1, PKN, ...
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Disease relevance of PKN1


Psychiatry related information on PKN1


High impact information on PKN1

  • When activated by extracellular signals via membrane signaling receptors, Rac executes its functions through engaging downstream effectors such as p21-activated kinase (PAK), a serine/threonine protein kinase [8].
  • In this issue, report direct communication between guanylyl cyclases and the Rac-p21-activated kinase (PAK) signaling pathway-which is essential for cell migration-to promote cell motility, through allosteric activation of guanylyl cyclases by autophosphorylated PAK [9].
  • This Rac/PAK/GC/cGMP pathway is involved in platelet-derived growth factor-induced fibroblast cell migration and lamellipodium formation [8].
  • Consequently, Nef, but not a Nef mutant incapable of activating PAK, blocked apoptosis in T cells induced by serum starvation or HIV replication [10].
  • MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1 [11].

Chemical compound and disease context of PKN1


Biological context of PKN1

  • A role for PKN1 in mediating arsenite-induced G(2)/M delay was supported by the finding that expression of a constitutively active form of PKN1 (PKN1AF3) in HeLa cells delayed the mitotic entry of cell cycle [17].
  • The transactivation unit 5 (TAU-5) located in the N-terminus of AR suffices for activation by PRK1 [1].
  • Phosphorylation events associated with different states of activation of a hepatic cardiolipin/protease-activated protein kinase. Structural identity to the protein kinase N-type protein kinases [18].
  • PKN is a fatty acid- and Rho-activated serine/threonine protein kinase, having a catalytic domain homologous to protein kinase C family [19].
  • Sigmoidal autophosphorylation kinetics and increased S6-(229-239) peptide kinase activity following preincubation with ATP suggested phosphorylation-dependent activation of PAK-1/PKN [18].

Anatomical context of PKN1

  • Cardiolipin- or protease-activated protein kinase, isolated from rat liver cytosol and originally named liver PAK-1, was found to be the natural form of protein kinase N (PKN) by comparing the sequences of 43 tryptic peptides of the purified liver enzyme and determining the corresponding liver cDNA sequence [18].
  • Both PRK1 and PRK2, expressed in COS 1 cells, are autophosphorylated in immunoprecipitates, indicating intrinsic kinase activity [20].
  • Here, we present evidence that identifies a novel plasma membrane pool of PRK1 [21].
  • The phosphorylation of serine377 of PRK1 is required for its integration into membranes [21].
  • PKN, a fatty acid- and Rho-activated serine/threonine kinase having a catalytic domain highly homologous to protein kinase C (PKC), was cleaved at specific sites in apoptotic Jurkat and U937 cells on Fas ligation and treatment with staurosporin or etoposide, respectively [22].

Associations of PKN1 with chemical compounds


Physical interactions of PKN1


Enzymatic interactions of PKN1

  • In addition to a direct interaction, PDK1 also phosphorylated Thr(774) in the activation loop and activated PKN [26].
  • HPr kinase/phosphorylases (HprKs) regulate catabolite repression and sugar transport in Gram-positive bacteria by phosphorylating the small phosphotransferase system (PTS) protein HPr on a serine residue [27].

Regulatory relationships of PKN1

  • PRK1 (PKN) is a serine/threonine kinase that has been shown to be activated by RhoA (Amano, M., Mukai, H., Ono, Y., Chihara, K., Matsui, T., Hamajima, Y., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) Science 271, 648-650) [28].
  • PKN regulates phospholipase D1 through direct interaction [29].
  • Analysis of the activation state of the components upstream of p38 and JNK showed that NSAIDs inhibit the serine-threonine kinase p21-activated protein kinase 1 (Pak1) and the small guanosine 5'-triphosphatase (GTPase) Rac, as well as the Rac-specific guanine nucleotide exchanger, Vav [30].
  • Moreover, Cdc25C is phosphorylated by the TGF-beta1-activated PKN [6].
  • Past work described the partial purification and characterization of a novel serine protein kinase activity designated protein kinase N (PKN) that is activated by nerve growth factor (NGF) in cultured PC12 cells [Rowland et al. (1987) J. Biol. Chem. 262; 7504-7513] [31].

Other interactions of PKN1

  • Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif [28].
  • Interaction of PKN with alpha-actinin [19].
  • These results suggest that the PKN family functions as a novel intracellular player of PLD1 signaling pathway [29].
  • Here we investigate the binding of PRK1 to RhoA and Rac1, two members of the Rho family [32].
  • PRK1 and PRK2, as well as a third member of this family, PRK3, show distinct patterns of expression in adult tissues [20].

Analytical, diagnostic and therapeutic context of PKN1


  1. A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer. Metzger, E., Müller, J.M., Ferrari, S., Buettner, R., Schüle, R. EMBO J. (2003) [Pubmed]
  2. PKN interacts with a paraneoplastic cerebellar degeneration-associated antigen, which is a potential transcription factor. Takanaga, H., Mukai, H., Shibata, H., Toshimori, M., Ono, Y. Exp. Cell Res. (1998) [Pubmed]
  3. 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. Bartsch, J.W., Mukai, H., Takahashi, N., Ronsiek, M., Fuchs, S., Jockusch, H., Ono, Y. Genomics (1998) [Pubmed]
  4. A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1. Haraga, A., Miller, S.I. Cell. Microbiol. (2006) [Pubmed]
  5. CD66-mediated phagocytosis of Opa52 Neisseria gonorrhoeae requires a Src-like tyrosine kinase- and Rac1-dependent signalling pathway. Hauck, C.R., Meyer, T.F., Lang, F., Gulbins, E. EMBO J. (1998) [Pubmed]
  6. PKN activation via transforming growth factor-beta1 (TGF-beta1) receptor signaling delays G2/M phase transition in vascular smooth muscle cells. Su, C., Deaton, R.A., Iglewsky, M.A., Valencia, T.G., Grant, S.R. Cell Cycle (2007) [Pubmed]
  7. Reduced protein kinase C immunoreactivity and altered protein phosphorylation in Alzheimer's disease fibroblasts. Van Huynh, T., Cole, G., Katzman, R., Huang, K.P., Saitoh, T. Arch. Neurol. (1989) [Pubmed]
  8. A Rac-cGMP Signaling Pathway. Guo, D., Tan, Y.C., Wang, D., Madhusoodanan, K.S., Zheng, Y., Maack, T., Zhang, J.J., Huang, X.Y. Cell (2007) [Pubmed]
  9. PAK-in' Up cGMP for the Move. Settleman, J. Cell (2007) [Pubmed]
  10. HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals. Wolf, D., Witte, V., Laffert, B., Blume, K., Stromer, E., Trapp, S., d'Aloja, P., Schürmann, A., Baur, A.S. Nat. Med. (2001) [Pubmed]
  11. Inhibition of myosin light chain kinase by p21-activated kinase. Sanders, L.C., Matsumura, F., Bokoch, G.M., de Lanerolle, P. Science (1999) [Pubmed]
  12. P21-activated kinase 1 regulation of estrogen receptor-alpha activation involves serine 305 activation linked with serine 118 phosphorylation. Rayala, S.K., Talukder, A.H., Balasenthil, S., Tharakan, R., Barnes, C.J., Wang, R.A., Aldaz, M., Khan, S., Kumar, R. Cancer Res. (2006) [Pubmed]
  13. NF-kappaB- and C/EBPbeta-driven interleukin-1beta gene expression and PAK1-mediated caspase-1 activation play essential roles in interleukin-1beta release from Helicobacter pylori lipopolysaccharide-stimulated macrophages. Basak, C., Pathak, S.K., Bhattacharyya, A., Mandal, D., Pathak, S., Kundu, M. J. Biol. Chem. (2005) [Pubmed]
  14. Cdc42 and RhoB activation are required for mannose receptor-mediated phagocytosis by human alveolar macrophages. Zhang, J., Zhu, J., Bu, X., Cushion, M., Kinane, T.B., Avraham, H., Koziel, H. Mol. Biol. Cell (2005) [Pubmed]
  15. Nicotine inhibits human gingival fibroblast migration via modulation of Rac signalling pathways. Fang, Y., Svoboda, K.K. Journal of clinical periodontology. (2005) [Pubmed]
  16. Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells. Mazumdar, A., Kumar, R. FEBS Lett. (2003) [Pubmed]
  17. Involvement of protein kinase PKN1 in G2/M delay caused by arsenite. Isagawa, T., Takahashi, M., Kato, T., Mukai, H., Ono, Y. Mol. Carcinog. (2005) [Pubmed]
  18. Phosphorylation events associated with different states of activation of a hepatic cardiolipin/protease-activated protein kinase. Structural identity to the protein kinase N-type protein kinases. Peng, B., Morrice, N.A., Groenen, L.C., Wettenhall, R.E. J. Biol. Chem. (1996) [Pubmed]
  19. Interaction of PKN with alpha-actinin. Mukai, H., Toshimori, M., Shibata, H., Takanaga, H., Kitagawa, M., Miyahara, M., Shimakawa, M., Ono, Y. J. Biol. Chem. (1997) [Pubmed]
  20. Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family. Palmer, R.H., Ridden, J., Parker, P.J. Eur. J. Biochem. (1995) [Pubmed]
  21. Signaling via a novel integral plasma membrane pool of a serine/threonine protein kinase PRK1 in mammalian cells. Zhu, Y., Stolz, D.B., Guo, F., Ross, M.A., Watkins, S.C., Tan, B.J., Qi, R.Z., Manser, E., Li, Q.T., Bay, B.H., Teo, T.S., Duan, W. FASEB J. (2004) [Pubmed]
  22. Proteolytic activation of PKN by caspase-3 or related protease during apoptosis. Takahashi, M., Mukai, H., Toshimori, M., Miyamoto, M., Ono, Y. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  23. Activation of the small GTPase Rac1 by cGMP-dependent protein kinase. Hou, Y., Ye, R.D., Browning, D.D. Cell. Signal. (2004) [Pubmed]
  24. Protein kinase C-related kinase and ROCK are required for thrombin-induced endothelial cell permeability downstream from Galpha12/13 and Galpha11/q. Gavard, J., Gutkind, J.S. J. Biol. Chem. (2008) [Pubmed]
  25. The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1. Maesaki, R., Ihara, K., Shimizu, T., Kuroda, S., Kaibuchi, K., Hakoshima, T. Mol. Cell (1999) [Pubmed]
  26. Phosphorylation of protein kinase N by phosphoinositide-dependent protein kinase-1 mediates insulin signals to the actin cytoskeleton. Dong, L.Q., Landa, L.R., Wick, M.J., Zhu, L., Mukai, H., Ono, Y., Liu, F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  27. Bioinformatic analyses of bacterial HPr kinase/phosphorylase homologues. Stonestrom, A., Barabote, R.D., Gonzalez, C.F., Saier, M.H. Res. Microbiol. (2005) [Pubmed]
  28. Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif. Flynn, P., Mellor, H., Palmer, R., Panayotou, G., Parker, P.J. J. Biol. Chem. (1998) [Pubmed]
  29. PKN regulates phospholipase D1 through direct interaction. Oishi, K., Takahashi, M., Mukai, H., Banno, Y., Nakashima, S., Kanaho, Y., Nozawa, Y., Ono, Y. J. Biol. Chem. (2001) [Pubmed]
  30. Nonsteroidal anti-inflammatory drugs inhibit a Fyn-dependent pathway coupled to Rac and stress kinase activation in TCR signaling. Paccani, S.R., Patrussi, L., Ulivieri, C., Masferrer, J.L., D'Elios, M.M., Baldari, C.T. Blood (2005) [Pubmed]
  31. Nerve growth factor (NGF) responses by non-neuronal cells: detection by assay of a novel NGF-activated protein kinase. Volonté, C., Greene, L.A. Growth Factors (1990) [Pubmed]
  32. Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1). Owen, D., Lowe, P.N., Nietlispach, D., Brosnan, C.E., Chirgadze, D.Y., Parker, P.J., Blundell, T.L., Mott, H.R. J. Biol. Chem. (2003) [Pubmed]
  33. Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus. Takahashi, M., Shibata, H., Shimakawa, M., Miyamoto, M., Mukai, H., Ono, Y. J. Biol. Chem. (1999) [Pubmed]
  34. p38 Mitogen-activated protein kinase mediates cell death and p21-activated kinase mediates cell survival during chemotherapeutic drug-induced mitotic arrest. Deacon, K., Mistry, P., Chernoff, J., Blank, J.L., Patel, R. Mol. Biol. Cell (2003) [Pubmed]
  35. Cloning and characterization of AWP1, a novel protein that associates with serine/threonine kinase PRK1 in vivo. Duan, W., Sun, B., Li, T.W., Tan, B.J., Lee, M.K., Teo, T.S. Gene (2000) [Pubmed]
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