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Gene Review

Pkn1  -  protein kinase N1

Rattus norvegicus

Synonyms: PAK-1, Pkn, Prk1, Prkcl1, Protease-activated kinase 1, ...
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Disease relevance of Pkn1

  • These data imply that although resiniferatoxin-induced translocation of protein kinase C in dorsal root ganglion neurones was mainly indirect, it also caused direct activation of a protein kinase C-like kinase in these cells [1].

High impact information on Pkn1

  • Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics [2].
  • Intense protein kinase C-like immunoreactivity in the neuron was observed both in the membrane and cytoplasm of the perikarya, dendrites, axons, and axon terminals, while weak immunoreaction was seen in the nuclei but almost never in the nucleoles [3].
  • PI3K, phospho (p)-PKB, and PAK were co-localized to the site of apical ES in the seminiferous epithelium of the rat testis in immunohistochemistry studies [4].
  • In PC12 cells, others have shown that 6-TG blocks nerve growth factor-induced neurite outgrowth and selectively inhibits the activity of protein kinase N, a partially characterized, nerve growth factor-inducible serine-threonine kinase [5].
  • Our findings suggest that (a) GTPgammaS and insulin activate Rho, PI 3-kinase, and PKN, albeit by different mechanisms; (b) each of these signaling substances appears to be required for, and may contribute to, increases in glucose transport; and (c) PKC-zeta may contribute to increases in glucose transport during insulin, but not GTPgammaS, action [6].

Biological context of Pkn1

  • PAK-1 has protein and peptide substrate specificities distinct from those of known protein kinase C isoforms and is insensitive to inhibition by the protein kinase C-alpha-(19-31) pseudosubstrate peptide [7].
  • Partial amino acid sequences of tryptic peptides derived from both the purified 116-kDa PAK-1 holoenzyme and its active catalytic fragment reveal that the catalytic domain is most related (50-58% identity) to the protein kinase C family [7].
  • Protein kinase N1 comprised one polypeptide of Mr 35,000 which underwent phosphorylation in the presence of Mg2+ + ATP [8].
  • C-PKA and PKN are widely expressed enzymes and the possibility of PKN-dependent modulation of PKA in intact cells would therefore have biological implications for signal transduction mechanisms [9].
  • Rho family small G-proteins Rac and Cdc42, and their immediate downstream effector p21-activated kinase (PAK), have been demonstrated to mediate important effects on the cytoskeleton that are relevant for cell migration and proliferation [10].

Anatomical context of Pkn1


Associations of Pkn1 with chemical compounds


Other interactions of Pkn1

  • The general S6 peptide substrate determinants for liver PAK-1 resembled those for brain protein kinase C and another major liver PAK, termed PAK-2 [15].
  • The substrate specificity determinants of a protease-activated protein kinase from rat liver, termined PAK-1, have been investigated using peptide analogues of the ribosomal protein S6 sequence: Ala229-Lys-Arg-Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala-Ser-Thr-Ser-Lys- Ser244 [15].


  1. Activation of protein kinase C by the capsaicin analogue resiniferatoxin in sensory neurones. Harvey, J.S., Davis, C., James, I.F., Burgess, G.M. J. Neurochem. (1995) [Pubmed]
  2. Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics. Nayal, A., Webb, D.J., Brown, C.M., Schaefer, E.M., Vicente-Manzanares, M., Horwitz, A.R. J. Cell Biol. (2006) [Pubmed]
  3. Distribution of protein kinase C-like immunoreactive neurons in rat brain. Saito, N., Kikkawa, U., Nishizuka, Y., Tanaka, C. J. Neurosci. (1988) [Pubmed]
  4. Sertoli-germ cell anchoring junction dynamics in the testis are regulated by an interplay of lipid and protein kinases. Siu, M.K., Wong, C.H., Lee, W.M., Cheng, C.Y. J. Biol. Chem. (2005) [Pubmed]
  5. Axon outgrowth is regulated by an intracellular purine-sensitive mechanism in retinal ganglion cells. Benowitz, L.I., Jing, Y., Tabibiazar, R., Jo, S.A., Petrausch, B., Stuermer, C.A., Rosenberg, P.A., Irwin, N. J. Biol. Chem. (1998) [Pubmed]
  6. Comparative effects of GTPgammaS and insulin on the activation of Rho, phosphatidylinositol 3-kinase, and protein kinase N in rat adipocytes. Relationship to glucose transport. Standaert, M., Bandyopadhyay, G., Galloway, L., Ono, Y., Mukai, H., Farese, R. J. Biol. Chem. (1998) [Pubmed]
  7. A cardiolipin-activated protein kinase from rat liver structurally distinct from the protein kinases C. Morrice, N.A., Gabrielli, B., Kemp, B.E., Wettenhall, R.E. J. Biol. Chem. (1994) [Pubmed]
  8. Purification of nuclear cAMP-independent protein kinases from rat ventral prostate. Goueli, S.A., Davis, A.T., Ahmed, K. Int. J. Biochem. (1986) [Pubmed]
  9. Nerve growth factor-activated protein kinase N modulates the cAMP-dependent protein kinase. Volonté, C., Greene, L.A. J. Neurosci. Res. (1995) [Pubmed]
  10. Lysophosphatidic acid stimulates p21-activated kinase in vascular smooth muscle cells. Schmitz, U., Thömmes, K., Beier, I., Vetter, H. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  11. Phosphorylation of cortactin by p21-activated kinase. Webb, B.A., Zhou, S., Eves, R., Shen, L., Jia, L., Mak, A.S. Arch. Biochem. Biophys. (2006) [Pubmed]
  12. A purine analog-sensitive protein kinase activity associates with Trk nerve growth factor receptors. Volonté, C., Loeb, D.M., Greene, L.A. J. Neurochem. (1993) [Pubmed]
  13. Protein kinase C in astrocytes: a determinant of cell morphology. Mobley, P.L., Scott, S.L., Cruz, E.G. Brain Res. (1986) [Pubmed]
  14. Association of a purine-analogue-sensitive protein kinase activity with p75 nerve growth factor receptors. Volonté, C., Ross, A.H., Greene, L.A. Mol. Biol. Cell (1993) [Pubmed]
  15. Determinants of multi-site phosphorylation of peptide analogues of ribosomal protein S6 by novel protease-activated protein kinases. Wettenhall, R.E., Gabrielli, B., Morrice, N., Bozinova, L., Kemp, B.E., Stapleton, D. Pept. Res. (1991) [Pubmed]
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