Atypical Protein Kinase Cι as a human oncogene and therapeutic target

Biochemical Pharmacology

Volumn 88, Issue 1, 2014, Pages 1-11

  Parker, Peter J ^b,c   Justilien, Verline ^a   Riou, Philippe ^b   Linch, Mark ^b,d   Fields, Alan P ^a  

^a MAYO CLINIC   (United States)

^b London Research Institute   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d ROYAL MARSDEN HOSPITAL   (United Kingdom)

Author keywords

Atypical Protein Kinase C ; Cellular transformation; Mechanism based therapeutics; Oncogenic signaling; Phox Bem1 (PB1) domain

Indexed keywords

CISPLATIN; GEMCITABINE; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PROTEIN KINASE C IOTA; RAPAMYCIN; VINCRISTINE; AURANOFIN; AUROTHIOGLUCOSE; AUROTHIOMALATE; RAC1 PROTEIN; URSOLIC ACID;

ARTICLE; CANCER CELL; CELL TRANSFORMATION; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME LOCALIZATION; GENE OVEREXPRESSION; HUMAN; MOLECULARLY TARGETED THERAPY; NEOPLASM; NONHUMAN; ONCOGENE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; APOPTOSIS; BILE DUCT TUMOR; BINDING AFFINITY; BLADDER CARCINOMA; BRAIN TUMOR; BREAST ADENOCARCINOMA; CANCER SURVIVAL; CANCER THERAPY; CELL SURVIVAL; COLON TUMOR; COPY NUMBER VARIATION; ENZYME ACTIVE SITE; ENZYME PHOSPHORYLATION; ESOPHAGUS TUMOR; GENE AMPLIFICATION; GENE DOSAGE; GENE EXPRESSION; KIDNEY CARCINOMA; LIVER TUMOR; LUNG ADENOCARCINOMA; LUNG SQUAMOUS CELL CARCINOMA; MELANOMA; NUCLEAR LOCALIZATION SIGNAL; OVARY CARCINOMA; OVARY TUMOR; PANCREAS TUMOR; PDZ DOMAIN; RHABDOMYOSARCOMA; SOMATIC MUTATION;

ATYPICAL PROTEIN KINASE CΙ; CELLULAR TRANSFORMATION; MECHANISM-BASED THERAPEUTICS; ONCOGENIC SIGNALING; PHOX-BEM1 (PB1) DOMAIN;

ANIMALS; CELL SURVIVAL; HUMANS; ISOENZYMES; MOLECULAR TARGETED THERAPY; NEOPLASMS; ONCOGENES; PROTEIN KINASE C; PROTEIN KINASE INHIBITORS; SIGNAL TRANSDUCTION;

EID: 84896733184     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2013.10.023     Document Type: Note

References (102)

1. H. Mellor, and P.J. Parker The extended protein kinase C superfamily Biochem J 332 Pt 2 1998 281 292 [Epub 1998/06/26. PubMed PMID: 9601053; PubMed Central PMCID: PMC1219479] (Pubitemid 28271856)
2. Y. Takai, A. Kishimoto, Y. Iwasa, Y. Kawahara, T. Mori, and Y. Nishizuka Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids J Biol Chem 254 10 1979 3692 3695 [Epub 1979/05/25. PubMed PMID: 438153]
3. Y. Ono, T. Fujii, K. Ogita, U. Kikkawa, K. Igarashi, and Y. Nishizuka The structure, expression, and properties of additional members of the protein kinase C family J Biol Chem 263 14 1988 6927 6932 [Epub 1988/05/15. PubMed PMID: 2834397]
4. Y. Ono, T. Fujii, K. Ogita, U. Kikkawa, K. Igarashi, and Y. Nishizuka Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties Proc Natl Acad Sci U S A 86 9 1989 3099 3103 [PubMed PMID: 2470089] (Pubitemid 19129566)
5. L.A. Selbie, C. Schmitz-Peiffer, Y. Sheng, and T.J. Biden Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells J Biol Chem 268 32 1993 24296 24302 [PubMed PMID: 8226978] (Pubitemid 23335419)
6. H. Mukai, M. Kitagawa, H. Shibata, H. Takanaga, K. Mori, and M. Shimakawa et al. Activation of PKN, a novel 120-kDa protein kinase with leucine zipper-like sequences, by unsaturated fatty acids and by limited proteolysis Biochem Biophys Res Commun 204 1 1994 348 356 [Epub 1994/10/14. doi: S0006-291X(84)72466-1 [pii] 10.1006/bbrc.1994.2466. PubMed PMID: 7945381] (Pubitemid 24335302)
7. R.H. Palmer, J. Ridden, and P.J. Parker Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family Eur J Biochem 227 1-2 1995 344 351 [Epub 1995/01/15. PubMed PMID: 7851406]
8. M.E. Reyland Protein kinase C isoforms: multi-functional regulators of cell life and death Front Biosci (Landmark Ed). 14 2009 2386 2399 [Epub 2009/03/11. doi: 3385 [pii]. PubMed PMID: 19273207]
9. C. Rosse, M. Linch, S. Kermorgant, A.J. Cameron, K. Boeckeler, and P.J. Parker PKC and the control of localized signal dynamics Nat Rev Mol Cell Biol 11 2 2010 103 112 [Epub 2010/01/23. doi: 10.1038/nrm2847. nrm2847 [pii]. PubMed PMID: 20094051]
10. A.P. Fields, and N.R. Murray Protein kinase C isozymes as therapeutic targets for treatment of human cancers Adv Enzyme Regul 48 2008 166 178 [Epub 2008/01/03. doi: 10.1016/j.advenzreg.2007.11.014. S0065-2571(07)00055-6 [pii]. PubMed PMID: 18167314; PubMed Central PMCID: PMC2586109]
11. M. Leitges Functional PKC in vivo analysis using deficient mouse models Biochem Soc Trans 35 Pt 5 2007 1018 1020 [Epub 2007/10/25. doi: BST0351018 [pii] 10.1042/BST0351018. PubMed PMID: 17956267] (Pubitemid 350206417)
12. A.W. Poole, G. Pula, I. Hers, D. Crosby, and M.L. Jones PKC-interacting proteins: from function to pharmacology Trends Pharmacol Sci 25 10 2004 528 535 [Epub 2004/09/24. doi: 10.1016/j.tips.2004.08.006 S0165-6147(04)00229-9 [pii]. PubMed PMID: 15380937] (Pubitemid 39236444)
13. A.P. Fields, N.R. Murray, and W.C. Gustafson Characterization of the role of protein kinase C isozymes in colon carcinogenesis using transgenic mouse models Methods Mol Biol 233 2003 539 553 [PubMed PMID: 12840533]
14. R.P. Regala, C. Weems, L. Jamieson, A. Khoor, E.S. Edell, and C.M. Lohse et al. Atypical protein kinase C iota is an oncogene in human non-small cell lung cancer Cancer Res 65 19 2005 8905 8911 [Epub 2005/10/06. doi: 65/19/8905 [pii] 10.1158/0008-5472.CAN-05-2372. PubMed PMID: 16204062] (Pubitemid 41377380)
15. A.M. Eder, X. Sui, D.G. Rosen, L.K. Nolden, K.W. Cheng, and J.P. Lahad et al. Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer Proc Natl Acad Sci U S A 102 35 2005 12519 12524 [PubMed PMID: 16116079] (Pubitemid 41266391)
16. M. Inoue, A. Kishimoto, Y. Takai, and Y. Nishizuka Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. II. Proenzyme and its activation by calcium-dependent protease from rat brain J Biol Chem 252 21 1977 7610 7616 [Epub 1977/11/10. PubMed PMID: 199594] (Pubitemid 8227337)
17. A.J. Cameron, M. De Rycker, V. Calleja, D. Alcor, S. Kjaer, and B. Kostelecky et al. Protein kinases, from B to C Biochem Soc Trans 35 Pt 5 2007 1013 1017 [Epub 2007/10/25. doi: BST0351013 [pii]. 10.1042/BST0351013. PubMed PMID: 17956266] (Pubitemid 350206416)
18. A.C. Newton The ins and outs of protein kinase C Methods Mol Biol 233 2003 3 7 [Epub 2003/07/04. doi: 1-59259-397-6-3 [pii] 10.1385/1-59259-397-6:3. PubMed PMID: 12840493]
19. L.A. Lopez-Garcia, J.O. Schulze, W. Frohner, H. Zhang, E. Suss, and N. Weber et al. Allosteric regulation of protein kinase PKCzeta by the N-terminal C1 domain and small compounds to the PIF-pocket Chem Biol 18 11 2011 1463 1473 [Epub 2011/11/29. doi: S1074-5521(11)00319-X [pii] 10.1016/j.chembiol.2011.08. 010. PubMed PMID: 22118680]
20. E.A. Nalefski, and A.C. Newton Membrane binding kinetics of protein kinase C betaII mediated by the C2 domain Biochemistry 40 44 2001 13216 13229 [Epub 2001/10/31. doi: bi010761u [pii]. PubMed PMID: 11683630] (Pubitemid 33043536)
21. T.A. Leonard, B. Rozycki, L.F. Saidi, G. Hummer, and J.H. Hurley Crystal structure and allosteric activation of protein kinase C beta II Cell 144 1 2011 55 66 [Epub 2011/01/11. doi: 10.1016/j.cell.2010.12.013 S0092-8674(10)01431-5 [pii]. PubMed PMID: 21215369; PubMed Central PMCID: PMC3104240]
22. T. Takimura, K. Kamata, K. Fukasawa, H. Ohsawa, H. Komatani, and T. Yoshizumi et al. Structures of the PKC-iota kinase domain in its ATP-bound and apo forms reveal defined structures of residues 533-551 in the C-terminal tail and their roles in ATP binding Acta Crystallogr D Biol Crystallogr 66 Pt 5 2010 577 583 [Epub 2010/05/07. doi: 10.1107/S0907444910005639 [0907444910005639S] [pii]. PubMed PMID: 20445233]
23. R.V. Stahelin, K.F. Kong, S. Raha, W. Tian, H.R. Melowic, and K.E. Ward et al. Protein kinase Ctheta C2 domain is a phosphotyrosine binding module that plays a key role in its activation J Biol Chem 287 36 2012 30518 30528 [Epub 2012/07/13. doi: 10.1074/jbc.M112.391557 M112.391557 [pii]. PubMed PMID: 22787157; PubMed Central PMCID: PMC3436300]
24. G.R. Budas, T. Koyanagi, E.N. Churchill, and D. Mochly-Rosen Competitive inhibitors and allosteric activators of protein kinase C isoenzymes: a personal account and progress report on transferring academic discoveries to the clinic Biochem Soc Trans 35 Pt 5 2007 1021 1026 [Epub 2007/10/25. doi: BST0351021 [pii] 10.1042/BST0351021. PubMed PMID: 17956268] (Pubitemid 350206418)
25. E.J. Welch, B.W. Jones, and J.D. Scott Networking with AKAPs: context-dependent regulation of anchored enzymes Mol Interv 10 2 2010 86 97 [Epub 2010/04/07. doi: 10.1124/mi.10.2.6. 10/2/86 [pii]. PubMed PMID: 20368369; PubMed Central PMCID: PMC2895371]
26. K. Akimoto, K. Mizuno, S. Osada, S. Hirai, S. Tanuma, and K. Suzuki et al. A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells J Biol Chem 269 17 1994 12677 12683 [Epub 1994/04/29. PubMed PMID: 7513693] (Pubitemid 24202058)
27. H. Nakanishi, K.A. Brewer, and J.H. Exton Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate J Biol Chem 268 1 1993 13 16 [PubMed PMID: 8380153] (Pubitemid 23021278)
28. J. Moscat, M.T. Diaz-Meco, A. Albert, and S. Campuzano Cell signaling and function organized by PB1 domain interactions Mol Cell 23 5 2006 631 640 [PubMed PMID: 16949360] (Pubitemid 44292560)
29. M.W. Wooten, M.L. Seibenhener, V. Mamidipudi, M.T. Diaz-Meco, P.A. Barker, and J. Moscat The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor J Biol Chem 276 11 2001 7709 7712 [PubMed PMID: 11244088]
30. W.O. White, M.L. Seibenhener, and M.W. Wooten Phosphorylation of tyrosine 256 facilitates nuclear import of atypical protein kinase C J Cell Biochem 85 1 2002 42 53 [Epub 2002/03/14. doi: 10.1002/jcb.10101 [pii]. PubMed PMID: 11891849] (Pubitemid 34204068)
31. E.J. Tisdale Rab2 requires PKC iota/lambda to recruit beta-COP for vesicle formation Traffic 1 9 2000 702 712 [Epub 2001/02/24. doi: tra010903 [pii]. PubMed PMID: 11208158]
32. I.S. Samuels, M.L. Seibenhener, K.B. Neidigh, and M.W. Wooten Nerve growth factor stimulates the interaction of ZIP/p62 with atypical protein kinase C and targets endosomal localization: evidence for regulation of nerve growth factor-induced differentiation J Cell Biochem 82 3 2001 452 466 [Epub 2001/08/14. doi: 10.1002/jcb.1177 [pii]. PubMed PMID: 11500922] (Pubitemid 32729409)
33. B. Macek, C. Benda, A. Jestel, K. Maskos, M. Mann, and A. Messerschmidt Phosphorylation of the human full-length protein kinase Ciota J Proteome Res 7 7 2008 2928 2935 [Epub 2008/05/21. doi: 10.1021/pr800052z. PubMed PMID: 18489133]
34. V. Justilien, and A.P. Fields Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular transformation Oncogene 28 41 2009 3597 3607 [Epub 2009/07/21. doi: onc2009217 [pii]. 10.1038/onc.2009.217. PubMed PMID: 19617897; PubMed Central PMCID: PMC2762483]
35. L.A. Frederick, J.A. Matthews, L. Jamieson, V. Justilien, E.A. Thompson, and D.C. Radisky et al. Matrix metalloproteinase-10 is a critical effector of protein kinase Ciota-Par6alpha-mediated lung cancer Oncogene 27 35 2008 4841 4853 [Epub 2008/04/23. doi: onc2008119 [pii]. 10.1038/onc.2008.119. PubMed PMID: 18427549; PubMed Central PMCID: PMC2750877]
36. R.P. Regala, C. Weems, L. Jamieson, J.A. Copland, E.A. Thompson, and A.P. Fields Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity J Biol Chem 280 35 2005 31109 31115 [Epub 2005/07/05. doi: M505402200 [pii] 10.1074/jbc.M505402200. PubMed PMID: 15994303] (Pubitemid 41291846)
37. N.R. Murray, L. Jamieson, W. Yu, J. Zhang, Y. Gokmen-Polar, and D. Sier et al. Protein kinase C{iota} is required for Ras transformation and colon carcinogenesis in vivo J Cell Biol 164 6 2004 797 802 [PubMed PMID: 15024028] (Pubitemid 38366891)
38. L. Jamieson, L. Carpenter, T.J. Biden, and A.P. Fields Protein kinase Ciota activity is necessary for Bcr-Abl-mediated resistance to drug-induced apoptosis J Biol Chem 274 1999 3927 3930
39. J. Chen, and M. Zhang The Par3/Par6/aPKC complex and epithelial cell polarity Exp Cell Res 319 10 2013 1357 1364 [Epub 2013/03/29. doi: 10.1016/j.yexcr.2013.03.021 S0014-4827(13)00129-8 [pii]. PubMed PMID: 23535009]
40. Y. Hirano, S. Yoshinaga, R. Takeya, N.N. Suzuki, M. Horiuchi, and M. Kohjima et al. Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains J Biol Chem 280 10 2005 9653 9661 [Epub 2004/12/14. doi: M409823200 [pii] 10.1074/jbc.M409823200. PubMed PMID: 15590654] (Pubitemid 40409663)
41. L. Huang, and S.K. Muthuswamy Polarity protein alterations in carcinoma: a focus on emerging roles for polarity regulators Curr Opin Genet Dev 20 1 2010 41 50 [Epub 2010/01/23. doi: 10.1016/j.gde.2009.12.001 S0959-437X(09)00198-1 [pii]. PubMed PMID: 20093003; PubMed Central PMCID: PMC3015045]
42. T.A. Martin, M.D. Mason, and W.G. Jiang Tight junctions in cancer metastasis Front Biosci (Landmark Ed) 16 2011 898 936 [Epub 2011/01/05. doi: 3726 [pii]. PubMed PMID: 21196209]
43. G.S. Du, J.M. Wang, J.X. Lu, Q. Li, C.Q. Ma, and J.T. Du et al. Expression of P-aPKC-iota, E-cadherin, and beta-catenin related to invasion and metastasis in hepatocellular carcinoma Ann Surg Oncol 16 6 2009 1578 1586 [Epub 2009/03/18. doi: 10.1245/s10434-009-0423-7. PubMed PMID: 19290490]
44. Y. Kojima, K. Akimoto, Y. Nagashima, H. Ishiguro, S. Shirai, and T. Chishima et al. The overexpression and altered localization of the atypical protein kinase C lambda/iota in breast cancer correlates with the pathologic type of these tumors Hum Pathol 39 6 2008 824 831 [Epub 2008/06/10. doi: S0046-8177(07)00603-X [pii] 10.1016/j.humpath.2007.11.001. PubMed PMID: 18538170] (Pubitemid 351758943)
45. E. Erdogan, T. Lamark, M. Stallings-Mann, J. Lee, M. Pellecchia, and E.A. Thompson et al. Aurothiomalate inhibits transformed growth by targeting the PB1 domain of protein kinase Ciota J Biol Chem 281 38 2006 28450 28459 [Epub 2006/07/25. doi: M606054200 [pii] 10.1074/jbc.M606054200.;1; PubMed PMID: 16861740] (Pubitemid 44414558)
46. V. Aranda, T. Haire, M.E. Nolan, J.P. Calarco, A.Z. Rosenberg, and J.P. Fawcett et al. Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control Nat. Cell Biol. 8 11 2006 1235 1245 [PubMed PMID: 17060907] (Pubitemid 44660588)
47. V. Justilien, L. Jameison, C.J. Der, K.L. Rossman, and A.P. Fields Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation J Biol Chem 286 10 2011 8149 8157 [Epub 2010/12/30. doi: M110.196113 [pii] 10.1074/jbc.M110.196113. PubMed PMID: 21189248; PubMed Central PMCID: PMC3048701]
48. Y.L. Yang, J.Y. Chu, M.L. Luo, Y.P. Wu, Y. Zhang, and Y.B. Feng et al. Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma Genes Chromosomes Cancer 47 2 2008 127 136 [PubMed PMID: 17990328]
49. M. Linch, M. Sanz-Garcia, E. Soriano, Y. Zhang, P. Riou, and C. Rosse et al. A cancer-associated mutation in atypical protein kinase Cι occurs in a substrate-specific recruitment motif Sci Signal 6 293 2013 ra82 10.1126/scisignal.2004068 [PubMed PMID: 24045153]
50. N.R. Murray, K.R. Kalari, and A.P. Fields Protein kinase Ciota expression and oncogenic signaling mechanisms in cancer J Cell Physiol 226 4 2011 879 887 [Epub 2010/10/15. doi: 10.1002/jcp.22463. PubMed PMID: 20945390; PubMed Central PMCID: PMC3075823]
51. K. Kikuchi, A. Soundararajan, L.A. Zarzabal, C.R. Weems, L.D. Nelon, and S.T. Hampton et al. Protein kinase C iota as a therapeutic target in alveolar rhabdomyosarcoma Oncogene 32 3 2013 286 295 [Epub 2012/02/22. doi: 10.1038/onc.2012.46 onc201246 [pii]. PubMed PMID: 22349825; PubMed Central PMCID: PMC3360112]
52. J.D. Evans, P.A. Cornford, A. Dodson, J.P. Neoptolemos, and C.S. Foster Expression patterns of protein kinase C isoenzymes are characteristically modulated in chronic pancreatitis and pancreatic cancer Am J Clin Pathol 119 3 2003 392 402 [Epub 2003/03/21. PubMed PMID: 12645342] (Pubitemid 37047863)
53. M.L. Scotti, W.R. Bamlet, T.C. Smyrk, A.P. Fields, and N.R. Murray Protein kinase Cι is required for pancreatic cancer cell transformed growth and tumorigenesis Cancer Res 70 5 2010 2064 2074 10.1158/0008-5472.can-09-2684
54. W.C. Gustafson, S. Ray, L. Jamieson, E.A. Thompson, A.R. Brasier, and A.P. Fields Bcr-Abl regulates protein kinase Ciota (PKCiota) transcription via an Elk1 site in the PKCiota promoter J Biol Chem 279 10 2004 9400 9408 [PubMed PMID: 14670960] (Pubitemid 38296006)
55. H.W. Lee, L. Smith, G.R. Pettit, A. Vinitsky, and J.B. Smith Ubiquitination of protein kinase C-alpha and degradation by the proteasome J Biol Chem 271 35 1996 20973 20976 [Epub 1996/08/30. PubMed PMID: 8702857] (Pubitemid 26292937)
56. S.G. Liu, B.S. Wang, Y.Y. Jiang, T.T. Zhang, Z.Z. Shi, and Y. Yang et al. Atypical protein kinase Ciota (PKCiota) promotes metastasis of esophageal squamous cell carcinoma by enhancing resistance to Anoikis via PKCiota-SKP2-AKT pathway Mol Cancer Res 9 4 2011 390 402 [Epub 2011/02/12. doi: 10.1158/1541-7786.MCR-10-0359.1541-7786.MCR-10-0359 [pii]. PubMed PMID: 21310827]
57. R. Takagawa, K. Akimoto, Y. Ichikawa, H. Akiyama, Y. Kojima, and H. Ishiguro et al. High expression of atypical protein kinase C lambda/iota in gastric cancer as a prognostic factor for recurrence Ann Surg Oncol 17 1 2010 81 88 [Epub 2009/09/24. doi: 10.1245/s10434-009-0708-x. PubMed PMID: 19774416]
58. A.P. Fields, L.A. Frederick, and R.P. Regala Targeting the oncogenic protein kinase Ciota signalling pathway for the treatment of cancer Biochem Soc Trans 35 Pt 5 2007 996 1000 [PubMed PMID: 17956262] (Pubitemid 350206412)
59. L. Zhang, J. Huang, N. Yang, S. Liang, A. Barchetti, and A. Giannakakis et al. Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma Cancer Res 66 9 2006 4627 4635 [PubMed PMID: 16651413]
60. R.P. Regala, R.K. Davis, A. Kunz, A. Khoor, M. Leitges, and A.P. Fields Atypical protein kinase C{iota} is required for bronchioalveolar stem cell expansion and lung tumorigenesis Cancer Res 69 19 2009 7603 7611 [Epub 2009/09/10. doi: 10.1158/0008-5472.CAN-09-2066 0008-5472.CAN-09-2066 [pii]. PubMed PMID: 19738040; PubMed Central PMCID: PMC2756303]
61. T. Takayama, S. Katsuki, Y. Takahashi, M. Ohi, S. Nojiri, and S. Sakamaki et al. Aberrant crypt foci of the colon as precursors of adenoma and cancer N Engl J Med 339 18 1998 1277 1284 [PubMed PMID: 9791143] (Pubitemid 28496193)
62. N.R. Murray, L. Jamieson, W. Yu, J. Zhang, Y. Gokmen-Polar, and D. Sier et al. Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo J Cell Biol 164 6 2004 797 802 [PubMed PMID: 15024028] (Pubitemid 38366891)
63. C.F. Kim, E.L. Jackson, A.E. Woolfenden, S. Lawrence, I. Babar, and S. Vogel et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer Cell 121 6 2005 823 835 [PubMed PMID: 15960971] (Pubitemid 40806415)
64. Z. Jin, M. Xin, and X. Deng Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase J Biol Chem 280 16 2005 16045 16052 [Epub 2005/02/12. doi: M413488200 [pii]. 10.1074/jbc.M413488200. PubMed PMID: 15705582] (Pubitemid 40616729)
65. T. Kobayashi, T. Inoue, Y. Shimizu, N. Terada, A. Maeno, and Y. Kajita et al. Activation of Rac1 is closely related to androgen-independent cell proliferation of prostate cancer cells both in vitro and in vivo Mol Endocrinol 24 4 2010 722 734 [Epub 2010/03/06. doi: 10.1210/me. 2009-0326 me.2009-0326 [pii]. PubMed PMID: 20203103]
66. E.M. Rodriguez, E.E. Dunham, and G.S. Martin Atypical protein kinase C activity is required for extracellular matrix degradation and invasion by Src-transformed cells J Cell Physiol 221 1 2009 171 182 [Epub 2009/06/06. doi: 10.1002/jcp.21841. PubMed PMID: 19492416; PubMed Central PMCID: PMC2782718]
67. M.L. Standaert, G. Bandyopadhyay, Y. Kanoh, M.P. Sajan, and R.V. Farese Insulin and PIP3 activate PKC-zeta by mechanisms that are both dependent and independent of phosphorylation of activation loop (T410) and autophosphorylation (T560) sites Biochemistry 40 1 2001 249 255 [Epub 2001/01/05. doi: bi0018234 [pii]. PubMed PMID: 11141077] (Pubitemid 32052698)
68. P. Pillai, S. Desai, R. Patel, M. Sajan, R. Farese, and D. Ostrov et al. A novel PKC-iota inhibitor abrogates cell proliferation and induces apoptosis in neuroblastoma Int J Biochem Cell Biol 43 5 2011 784 794 [Epub 2011/02/15. doi: 10.1016/j.biocel.2011.02.002 S1357-2725(11)00042-2 [pii]. PubMed PMID: 21315177]
69. J.C. Shultz, N. Vu, M.D. Shultz, M.U. Mba, B.A. Shapiro, and C.E. Chalfant The Proto-oncogene PKCiota regulates the alternative splicing of Bcl-x pre-mRNA Mol Cancer Res 10 5 2012 660 669 [Epub 2012/04/24. doi: 10.1158/1541-7786.MCR-11-0363. 1541-7786.MCR-11-0363 [pii]. PubMed PMID: 22522453; PubMed Central PMCID: PMC3356487]
70. N.R. Murray, and A.P. Fields Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis J Biol Chem 272 44 1997 27521 27524 [PubMed PMID: 9346882] (Pubitemid 27473538)
71. H.Y. Win, and M. Acevedo-Duncan Atypical protein kinase C phosphorylates IKKαβ in transformed non-malignant and malignant prostate cell survival Cancer Lett 270 2 2008 302 311 10.1016/j.canlet.2008.05.023
72. Y. Lu, L. Jamieson, A.R. Brasier, and A.P. Fields NF-kappaB/RelA transactivation is required for atypical protein kinase C iota-mediated cell survival Oncogene 20 35 2001 4777 4792 (Pubitemid 32803149)
73. R.M. Baldwin, M. Garratt-Lalonde, D.A. Parolin, P.M. Krzyzanowski, M.A. Andrade, and I.A. Lorimer Protection of glioblastoma cells from cisplatin cytotoxicity via protein kinase Ciota-mediated attenuation of p38 MAP kinase signaling Oncogene 25 20 2006 2909 2919 [Epub 2005/12/07. doi: 1209312 [pii]. 10.1038/sj.onc.1209312. PubMed PMID: 16331246] (Pubitemid 43739241)
74. X. Wang, J. Nie, Q. Zhou, W. Liu, F. Zhu, and W. Chen et al. Downregulation of Par-3 expression and disruption of Par complex integrity by TGF-beta during the process of epithelial to mesenchymal transition in rat proximal epithelial cells Biochim Biophys Acta 1782 1 2008 51 59 [Epub 2007/12/12. doi: S0925-4439(07)00198-6 [pii] 10.1016/j.bbadis.2007.11.002. PubMed PMID: 18070611]
75. L.M. McCaffrey, J. Montalbano, C. Mihai, and I.G. Macara Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis Cancer Cell 22 5 2012 601 614 [Epub 2012/11/17 doi: 10.1016/j.ccr.2012.10.003. S1535-6108(12)00437-0 [pii]. PubMed PMID: 23153534; PubMed Central PMCID: PMC3500525]
76. A. Gunaratne, B.L. Thai, and G.M. Di Guglielmo Atypical protein kinase C phosphorylates Par6 and facilitates transforming growth factor beta-induced epithelial-to-mesenchymal transition Mol Cell Biol 33 5 2013 874 886 [Epub 2012/12/20. doi: 10.1128/MCB. 00837-12 MCB.00837-12 [pii]. PubMed PMID: 23249950; PubMed Central PMCID: PMC3623079]
77. R.M. Baldwin, D.A.E. Parolin, and I.A.J. Lorimer Regulation of glioblastoma cell invasion by PKC[iota] and RhoB Oncogene 27 25 2008 3587 3595 (Pubitemid 351793806)
78. R.P. Regala, V. Justilien, M.P. Walsh, C. Weems, A. Khoor, and N.R. Murray et al. Matrix metalloproteinase-10 promotes Kras-mediated bronchio-alveolar stem cell expansion and lung cancer formation PLoS ONE 6 10 2011 e26439 [Epub 2011/10/25. doi: 10.1371/journal.pone.0026439 PONE-D-11-14143 [pii]. PubMed PMID: 22022614; PubMed Central PMCID: PMC3195727]
79. E. Erdogan, E.W. Klee, E.A. Thompson, and A.P. Fields Meta-analysis of oncogenic protein kinase Cι signaling in lung adenocarcinoma Clin Cancer Res 15 5 2009 1527 1533 10.1158/1078-0432.ccr-08-2459
80. J. Rodon, R. Dienstmann, V. Serra, and J. Tabernero Development of PI3K inhibitors: lessons learned from early clinical trials Nat Rev Clin Oncol 10 3 2013 143 153 [Epub 2013/02/13. doi: 10.1038/nrclinonc.2013.10. nrclinonc.2013.10 [pii]. PubMed PMID: 23400000]
81. S.P. Davies, H. Reddy, M. Caivano, and P. Cohen Specificity and mechanism of action of some commonly used protein kinase inhibitors Biochem J 351 Pt 1 2000 95 105 [Epub 2000/09/22. PubMed PMID: 10998351; PubMed Central PMCID: PMC1221339]
82. A. Najafov, E.M. Sommer, J.M. Axten, M.P. Deyoung, and D.R. Alessi Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1 Biochem J 433 2 2011 357 369 [Epub 2010/11/23. doi: 10.1042/BJ20101732 [20101732BJ] [pii]. PubMed PMID: 21087210]
83. A. Balendran, A. Casamayor, M. Deak, A. Paterson, P. Gaffney, and R. Currie et al. PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 Curr Biol 9 8 1999 393 404 [Epub 1999/05/05. doi: S0960982299801869 [pii]. PubMed PMID: 10226025] (Pubitemid 29205782)
84. W. Frohner, L.A. Lopez-Garcia, S. Neimanis, N. Weber, J. Navratil, and F. Maurer et al. 4-Benzimidazolyl-3-phenylbutanoic acids as novel PIF-pocket-targeting allosteric inhibitors of protein kinase PKCzeta J Med Chem 54 19 2011 6714 6723 [Epub 2011/08/26. doi: 10.1021/jm2005892. PubMed PMID: 21863889]
85. J. Heitman, N.R. Movva, and M.N. Hall Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast Science 253 5022 1991 905 909 [Epub 1991/08/23. PubMed PMID: 1715094] (Pubitemid 21917235)
86. A.J. Cameron, M.D. Linch, A.T. Saurin, and C. Escribano Parker PJ. mTORC2 targets AGC kinases through Sin1-dependent recruitment Biochem J 439 2 2011 287 297 [Epub 2011/08/03. doi: 10.1042/BJ20110678.[20110678BJ] [pii]. PubMed PMID: 21806543]
87. S.A. Wander, B.T. Hennessy, and J.M. Slingerland Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy J Clin Invest 121 4 2011 1231 1241 [Epub 2011/04/15. doi: 10.1172/JCI44145. [pii]. PubMed PMID: 21490404; PubMed Central PMCID: PMC3069769]
88. H.C. Huang, C.Y. Huang, S.Y. Lin-Shiau, and J.K. Lin Ursolic acid inhibits IL-1β or TNF-α-induced C6 glioma invasion through suppressing the association ZIP/p62 with PKC-ζ and downregulating the MMP-9 expression Mol Carcinog 48 6 2009 517 531 10.1002/mc.20490
89. C.M. Ma, S.Q. Cai, J.R. Cui, R.Q. Wang, P.F. Tu, and M. Hattori et al. The cytotoxic activity of ursolic acid derivatives Eur J Med Chem 40 6 2005 582 589 [Epub 2005/06/01. doi: S0223-5234(05)00002-4 [pii] 10.1016/j.ejmech.2005.01. 001. PubMed PMID: 15922841] (Pubitemid 40732527)
90. M.K. Shanmugam, X. Dai, A.P. Kumar, B.K. Tan, G. Sethi, and A. Bishayee Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies Biochem Pharmacol 85 11 2013 1579 1587 10.1016/j.bcp.2013.03.006 [PubMed PMID: 23499879]
91. M. Stallings-Mann, L. Jamieson, R.P. Regala, C. Weems, N.R. Murray, and A.P. Fields A novel small-molecule inhibitor of protein kinase Ciota blocks transformed growth of non-small-cell lung cancer cells Cancer Res 66 3 2006 1767 1774 [PubMed PMID: 16452237] (Pubitemid 43259962)
92. L. Messori, and G. Marcon Gold complexes in the treatment of rheumatoid arthritis Met Ions Biol Syst 41 2004 279 304 [Epub 2004/06/23. PubMed PMID: 15206120]
93. R.P. Regala, E.A. Thompson, and A.P. Fields Atypical protein kinase Cι expression and aurothiomalate sensitivity in human lung cancer cells Cancer Res 68 14 2008 5888 5895 10.1158/0008-5472.can-08-0438
94. M. Trani, A. Sorrentino, C. Busch, and M. Landstrom Pro-apoptotic effect of aurothiomalate in prostate cancer cells Cell Cycle 8 2 2009 306 313 [Epub 2009/01/24. doi: 7596 [pii]. PubMed PMID: 19164922]
95. A.S. Mansfield, A.P. Fields, A. Jatoi, Y. Qi, A.A. Adjei, and C. Erlichman et al. Phase I dose escalation study of the PKCiota inhibitor aurothiomalate for advanced non-small-cell lung cancer, ovarian cancer, and pancreatic cancer Anticancer Drugs 2013 [Epub 2013/08/22. doi: 10.1097/CAD.0000000000000009. PubMed PMID: 23962904]
96. T. Eichholtz, D.B. de Bont, J. de Widt, R.M. Liskamp, and H.L. Ploegh A myristoylated pseudosubstrate peptide, a novel protein kinase C inhibitor J Biol Chem 268 3 1993 1982 1986 [Epub 1993/01/25. PubMed PMID: 8420972] (Pubitemid 23033603)
97. D. Schaap, P.J. Parker, A. Bristol, R. Kriz, and J. Knopf Unique substrate specificity and regulatory properties of PKC-epsilon: a rationale for diversity FEBS Lett 243 2 1989 351 357 [Epub 1989/01/30. doi: 0014-5793(89)80160-7 [pii]. PubMed PMID: 2917656] (Pubitemid 19037504)
98. G. Martiny-Baron, M.G. Kazanietz, H. Mischak, P.M. Blumberg, G. Kochs, and H. Hug et al. Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976 J Biol Chem 268 13 1993 9194 9197 [Epub 1993/05/05. PubMed PMID: 8486620] (Pubitemid 23145960)
99. D. Toullec, P. Pianetti, H. Coste, P. Bellevergue, T. Grand-Perret, and M. Ajakane et al. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C J Biol Chem 266 24 1991 15771 15781 [Epub 1991/08/25. PubMed PMID: 1874734] (Pubitemid 21907725)
100. M. Gschwendt, S. Dieterich, J. Rennecke, W. Kittstein, H.J. Mueller, and F.J. Johannes Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase C isoenzymes FEBS Lett 392 2 1996 77 80 [PubMed PMID: 8772178] (Pubitemid 26276722)
101. S. Kjaer, M. Linch, A. Purkiss, B. Kostelecky, P.P. Knowles, and C. Rosse et al. Adenosine-binding motif mimicry and cellular effects of a thieno[2,3-d]pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes Biochem J 451 2 2013 329 342 10.1042/BJ20121871 [PubMed PMID: 23418854]
102. M. Linch, M. Sanz-Garcia, C. Rosse, P. Riou, N. Peel, and C. Madsen et al. Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids Carcinogenesis 2013 [Epub 2013/09/28. doi: bgt313 [pii] 10.1093/carcin/bgt313. PubMed PMID: 24072773]