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PKN2  -  protein kinase N2

Homo sapiens

Synonyms: PAK2, PKN gamma, PRK2, PRKCL2, PRO2042, ...
 
 
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Disease relevance of PKN2

  • Intra- and intersubtype alternative Pak2-activating structural motifs of human immunodeficiency virus type 1 Nef [1].
  • The identification of multiple Pak2-activating structural motifs that singly affect one Nef activity revealed a functional plasticity that has implications for future drug and vaccine design aimed at HIV-1 Nef and its effects on the deregulation of the immune system [1].
  • Effects of overexpression of Pkn2, a transmembrane protein serine/threonine kinase, on development of Myxococcus xanthus [2].
  • Cell surface receptor downmodulation was largely unaffected by mutations of all N-terminal basic residues, while the association of Nef with Pak2 kinase activity and its ability to augment virion infectivity correlated with its lysine-mediated raft incorporation [3].
 

High impact information on PKN2

  • Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis [4].
  • PRK2 is required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B, the phosphatase required for activation of mitotic cyclin/Cdk1 complexes at the G2/M transition [4].
  • We now report that PRK2/PKN2, a Ser/Thr kinase and Rho/Rac effector protein, is an essential regulator of both entry into mitosis and exit from cytokinesis in HeLa S3 cells [4].
  • A chimeric protein in which the carboxyl-terminal hydrophobic motif (HM) of SGK3 has been exchanged for the HM of PRK2 is constitutively active [5].
  • RSK1 is activated directly by interaction with YopM, and RSK1 kinase activity is required for YopM-stimulated PRK2 activity [6].
 

Chemical compound and disease context of PKN2

 

Biological context of PKN2

  • PIF is situated carboxy-terminal to the kinase domain of PRK2, and contains a consensus motif for phosphorylation by PDK2 similar to that found in PKBalpha, except that the residue equivalent to Ser473 is aspartic acid [7].
  • During early stages of apoptosis, the C-terminal region of PRK2 is cleaved from the inhibitory N-terminal region and can bind Akt [8].
  • Potential differences in the mechanism of activation between the catalytic regions of PKN and PRK2 are also discussed [9].
  • To assess the relative contribution of these Rho effectors to the effects of Y-27632, we compared the cytoskeletal phenotype, wound healing and neurite outgrowth in cells treated with Y-27632 or subjected to knockdown with ROCK-I, ROCK-II or PRK-2- specific siRNAs [10].
 

Anatomical context of PKN2

  • Both PRK1 and PRK2, expressed in COS 1 cells, are autophosphorylated in immunoprecipitates, indicating intrinsic kinase activity [11].
  • PRK2 is expressed in the immature oocyte and at least until germinal vesicle breakdown [12].
  • Studies with selective inhibitors suggested that a variety of phosphatases might be involved in the rapid dephosphorylation of Pak 2 at Thr(402) in stimulated neutrophils [13].
  • Localization of p21-activated protein kinase gamma-PAK/Pak2 in the endoplasmic reticulum is required for induction of cytostasis [14].
  • In neurite outgrowth assays, knockdown of ROCK-I, ROCK-II or PRK-2 enhances neurite lengths, however no individual knockdown stimulated neurite outgrowth as robustly as Y-27632 [10].
 

Associations of PKN2 with chemical compounds

  • PAK-2/PRK2 was also activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids [15].
  • In particular, we demonstrate that a conserved C-terminal cysteine of PRK2 is indispensable for the interaction with PTP-BL [16].
  • The protein-protein interaction between Akt and the PRK2 C-terminal region specifically down-modulates the protein kinase activities of Akt by inhibiting phosphorylation at threonine 308 and serine 473 of Akt [8].
  • Significantly, PRK2 is phosphorylated in vivo in response to 1-methyladenine which precedes MPF activation, making PRK2 a candidate regulator of early signaling events of meiotic maturation [12].
  • The effect of Pkn2 overexpression on development of M. xanthus was examined by expressing pkn2 under the control of a kanamycin promoter [2].
 

Enzymatic interactions of PKN2

 

Other interactions of PKN2

  • These results identify the first intracellular targets of YopM and suggest YopM acts to stimulate the activity of PRK2 and RSK1 [6].
  • PRK1 and PRK2, as well as a third member of this family, PRK3, show distinct patterns of expression in adult tissues [11].
  • The related HR1 motif is also found to confer RhoA binding activity to the only other fully cloned member of this kinase family, PRK2 [18].
 

Analytical, diagnostic and therapeutic context of PKN2

  • Rat myeloma RNA was used as the RT-PCR template because of its relative abundance in PAK-2/PRK2 mRNA compared with liver and other rat tissues [15].
  • Pkn2 was clearly detected by Western blot (immunoblot) analysis in the overexpression strain (the PKm/pkn2 strain) but could not be detected in the wild-type strain [2].
  • CONCLUSIONS: Post-operative pain was less in eyes treated with LASEK than eyes treated with PRK 2 hours following laser surgery [19].

References

  1. Intra- and intersubtype alternative Pak2-activating structural motifs of human immunodeficiency virus type 1 Nef. O'Neill, E., Baugh, L.L., Novitsky, V.A., Essex, M.E., Garcia, J.V. J. Virol. (2006) [Pubmed]
  2. Effects of overexpression of Pkn2, a transmembrane protein serine/threonine kinase, on development of Myxococcus xanthus. Udo, H., Inouye, M., Inouye, S. J. Bacteriol. (1996) [Pubmed]
  3. Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV-1(SF2) Nef. Giese, S.I., Woerz, I., Homann, S., Tibroni, N., Geyer, M., Fackler, O.T. Virology (2006) [Pubmed]
  4. Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis. Schmidt, A., Durgan, J., Magalhaes, A., Hall, A. EMBO J. (2007) [Pubmed]
  5. Role of the Phox homology domain and phosphorylation in activation of serum and glucocorticoid-regulated kinase-3. Tessier, M., Woodgett, J.R. J. Biol. Chem. (2006) [Pubmed]
  6. The yersinia virulence factor YopM forms a novel protein complex with two cellular kinases. McDonald, C., Vacratsis, P.O., Bliska, J.B., Dixon, J.E. J. Biol. Chem. (2003) [Pubmed]
  7. PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2. Balendran, A., Casamayor, A., Deak, M., Paterson, A., Gaffney, P., Currie, R., Downes, C.P., Alessi, D.R. Curr. Biol. (1999) [Pubmed]
  8. Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage. Koh, H., Lee, K.H., Kim, D., Kim, S., Kim, J.W., Chung, J. J. Biol. Chem. (2000) [Pubmed]
  9. Mutational analysis of the regulatory mechanism of PKN: the regulatory region of PKN contains an arachidonic acid-sensitive autoinhibitory domain. Yoshinaga, C., Mukai, H., Toshimori, M., Miyamoto, M., Ono, Y. J. Biochem. (1999) [Pubmed]
  10. Molecular characterization of the effects of Y-27632. Darenfed, H., Dayanandan, B., Zhang, T., Hsieh, S.H., Fournier, A.E., Mandato, C.A. Cell Motil. Cytoskeleton (2007) [Pubmed]
  11. 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]
  12. Phosphorylation of protein kinase C-related kinase PRK2 during meiotic maturation of starfish oocytes. Stapleton, G., Nguyen, C.P., Lease, K.A., Hille, M.B. Dev. Biol. (1998) [Pubmed]
  13. p21-activated kinase 2 in neutrophils can be regulated by phosphorylation at multiple sites and by a variety of protein phosphatases. Zhan, Q., Ge, Q., Ohira, T., Van Dyke, T., Badwey, J.A. J. Immunol. (2003) [Pubmed]
  14. Localization of p21-activated protein kinase gamma-PAK/Pak2 in the endoplasmic reticulum is required for induction of cytostasis. Huang, Z., Ling, J., Traugh, J.A. J. Biol. Chem. (2003) [Pubmed]
  15. Isolation and characterization of a structural homologue of human PRK2 from rat liver. Distinguishing substrate and lipid activator specificities. Yu, W., Liu, J., Morrice, N.A., Wettenhall, R.E. J. Biol. Chem. (1997) [Pubmed]
  16. The protein kinase C-related kinase PRK2 interacts with the protein tyrosine phosphatase PTP-BL via a novel PDZ domain binding motif. Gross, C., Heumann, R., Erdmann, K.S. FEBS Lett. (2001) [Pubmed]
  17. Protein kinase C-related kinase 2 phosphorylates the protein synthesis initiation factor eIF4E in starfish oocytes. Lee, S.J., Stapleton, G., Greene, J.H., Hille, M.B. Dev. Biol. (2000) [Pubmed]
  18. 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]
  19. A comparative study of post-operative pain in laser epithelial keratomileusis versus photorefractive keratectomy. Saleh, T.A., Almasri, M.A. The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland. (2003) [Pubmed]
 
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