Protein Kinase Cζ (PKCζ) : Activation Mechanisms and Cellular Functions

The zeta isotype of protein kinase C (PKCzeta) is a member of the atypical PKC subfamily and has been widely implicated in the regulation of cellular functions. Increasing evidence from studies using in vitro and in vivo systems points to PKCzeta as a key regulator of critical intracellular signaling pathways induced by various extracellular stimuli. The major activation pathway of PKCzeta depends on phosphatidylinositol (PI)-3,4,5-trisphosphate (PIP(3)), which is mainly produced by PI-3 kinase. 3'-PI-dependent protein kinase 1, which binds with high affinity to PIP(3), phosphorylates and activates PKCzeta. Many studies demonstrated the involvement of PKCzeta in the mitogen-activated protein kinase cascade, transcriptional factor NFkappaB activation, ribosomal S6-protein kinase signaling, and cell polarity. An important molecular event in a cell is the association of PKCzeta with other signaling molecules, as well as scaffold proteins, to form large complexes that regulate their pathways. The understanding of the mechanisms underlying PKCzeta-mediated control of intracellular signaling is beginning to provide important insights into the roles of PKCzeta in various cells.

[1]  今野 大治郎,et al.  The postsynaptic density and dendritic raft localization of PSD-Zip70, which contains an N-myristoylation sequence and leucine-zipper motifs , 2003 .

[2]  J. Blenis,et al.  Characterization of Phosphatidylinositol 3-Kinase-dependent Phosphorylation of the Hydrophobic Motif Site Thr389 in p70 S6 Kinase 1* , 2002, The Journal of Biological Chemistry.

[3]  Y. Nishizuka,et al.  Protein kinase C isotypes and their specific functions: prologue. , 2002, Journal of biochemistry.

[4]  M. Vasseur-Cognet,et al.  The Adapter Protein ZIP Binds Grb14 and Regulates Its Inhibitory Action on Insulin Signaling by Recruiting Protein Kinase Cζ , 2002, Molecular and Cellular Biology.

[5]  C. Hodgkinson,et al.  Characterization of PDK2 activity against protein kinase B gamma. , 2002, Biochemistry.

[6]  Pilar Martín,et al.  Role of ζPKC in B‐cell signaling and function , 2002 .

[7]  R. Farese,et al.  Function and dysfunction of aPKC isoforms for glucose transport in insulin-sensitive and insulin-resistant states. , 2002, American journal of physiology. Endocrinology and metabolism.

[8]  John F. Crary,et al.  Protein kinase Mζ is necessary and sufficient for LTP maintenance , 2002, Nature Neuroscience.

[9]  Todd Charlton Sacktor,et al.  Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster , 2002, Nature Neuroscience.

[10]  M. W. Wooten,et al.  Structure and functional properties of the ubiquitin binding protein p62 , 2002, FEBS letters.

[11]  G. Joberty,et al.  Assembly of Epithelial Tight Junctions Is Negatively Regulated by Par6 , 2002, Current Biology.

[12]  P. Parker,et al.  AGC protein kinase phosphorylation and protein kinase C. , 2001, Biochemical Society transactions.

[13]  Juan F. García,et al.  Targeted Disruption of the ζPKC Gene Results in the Impairment of the NF-κB Pathway , 2001 .

[14]  S. Ohno.  Intercellular junctions and cellular polarity: the PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity. , 2001, Current opinion in cell biology.

[15]  A. Hall,et al.  Integrin-Mediated Activation of Cdc42 Controls Cell Polarity in Migrating Astrocytes through PKCζ , 2001, Cell.

[16]  Hansjuerg Alder,et al.  FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Y. Nagai,et al.  PAR‐6 regulates aPKC activity in a novel way and mediates cell‐cell contact‐induced formation of the epithelial junctional complex , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[18]  A. Newton,et al.  Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. , 2001, Chemical reviews.

[19]  G. Bjørkøy,et al.  Nuclear Import and Export Signals Enable Rapid Nucleocytoplasmic Shuttling of the Atypical Protein Kinase C λ* , 2001, The Journal of Biological Chemistry.

[20]  T. Ohnishi,et al.  Atypical Protein Kinase C Is Involved in the Evolutionarily Conserved Par Protein Complex and Plays a Critical Role in Establishing Epithelia-Specific Junctional Structures , 2001, The Journal of cell biology.

[21]  P. Barker,et al.  The Atypical Protein Kinase C-interacting Protein p62 Is a Scaffold for NF-κB Activation by Nerve Growth Factor* , 2001, The Journal of Biological Chemistry.

[22]  M. Diaz-Meco,et al.  MEK5, a New Target of the Atypical Protein Kinase C Isoforms in Mitogenic Signaling , 2001, Molecular and Cellular Biology.

[23]  M. Sajan,et al.  Insulin and PIP3 activate PKC-zeta by mechanisms that are both dependent and independent of phosphorylation of activation loop (T410) and autophosphorylation (T560) sites. , 2001, Biochemistry.

[24]  C. T. Powell,et al.  Rat protein kinase c zeta gene contains alternative promoters for generation of dual transcripts with 5'-end heterogeneity. , 2000, DNA and cell biology.

[25]  D. Alessi,et al.  Further evidence that 3‐phosphoinositide‐dependent protein kinase‐1 (PDK1) is required for the stability and phosphorylation of protein kinase C (PKC) isoforms , 2000, FEBS letters.

[26]  G. Hunninghake,et al.  Protein Kinase C ζ Plays a Central Role in Activation of the p42/44 Mitogen-Activated Protein Kinase by Endotoxin in Alveolar Macrophages1 , 2000, The Journal of Immunology.

[27]  E. Knust,et al.  Drosophila Atypical Protein Kinase C Associates with Bazooka and Controls Polarity of Epithelia and Neuroblasts , 2000, The Journal of cell biology.

[28]  M. Kasuga,et al.  Inhibition of Insulin-induced Glucose Uptake by Atypical Protein Kinase C Isotype-specific Interacting Protein in 3T3-L1 Adipocytes* , 2000, The Journal of Biological Chemistry.

[29]  T. Pawson,et al.  A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity , 2000, Nature Cell Biology.

[30]  G. Joberty,et al.  The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42 , 2000, Nature Cell Biology.

[31]  H. Nakano,et al.  The atypical PKC‐interacting protein p62 channels NF‐κB activation by the IL‐1–TRAF6 pathway , 2000, The EMBO journal.

[32]  Wolfgang Ziegler,et al.  Multiple pathways control protein kinase C phosphorylation , 2000, The EMBO journal.

[33]  M. Li,et al.  Differential stimulation of PKC phosphorylation of potassium channels by ZIP1 and ZIP2. , 1999, Science.

[34]  Robert V Farese,et al.  Insulin Activates Protein Kinases C-ζ and C-λ by an Autophosphorylation-dependent Mechanism and Stimulates Their Translocation to GLUT4 Vesicles and Other Membrane Fractions in Rat Adipocytes* , 1999, The Journal of Biological Chemistry.

[35]  M. Diaz-Meco,et al.  The interaction of p62 with RIP links the atypical PKCs to NF‐κB activation , 1999, The EMBO journal.

[36]  J. Blenis,et al.  p70 S6 Kinase Is Regulated by Protein Kinase Cζ and Participates in a Phosphoinositide 3-Kinase-Regulated Signalling Complex , 1999, Molecular and Cellular Biology.

[37]  C. Croce,et al.  The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  A. Newton,et al.  Carboxyl-terminal Phosphorylation Regulates the Function and Subcellular Localization of Protein Kinase C βII* , 1999, The Journal of Biological Chemistry.

[39]  G. Bren,et al.  Activation of IκB Kinase β by Protein Kinase C Isoforms , 1999, Molecular and Cellular Biology.

[40]  C. Tokunaga,et al.  Mammalian Homologue of the Caenorhabditis elegans UNC-76 Protein Involved in Axonal Outgrowth Is a Protein Kinase C ζ–interacting Protein , 1999, The Journal of cell biology.

[41]  J. Avruch,et al.  Atypical protein kinase Clambda binds and regulates p70 S6 kinase. , 1998, The Biochemical journal.

[42]  Philip R. Cohen,et al.  Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. , 1998, Science.

[43]  A. Newton,et al.  Regulation of protein kinase C ζ by PI 3-kinase and PDK-1 , 1998, Current Biology.

[44]  F. Piano,et al.  Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans. , 1998, Development.

[45]  M. Diaz-Meco,et al.  Localization of Atypical Protein Kinase C Isoforms into Lysosome-Targeted Endosomes through Interaction with p62 , 1998, Molecular and Cellular Biology.

[46]  R. Farese,et al.  Protein Kinase C-ζ as a Downstream Effector of Phosphatidylinositol 3-Kinase during Insulin Stimulation in Rat Adipocytes , 1997, The Journal of Biological Chemistry.

[47]  F. McCormick,et al.  Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. , 1997, Science.

[48]  N. Reiner,et al.  Phosphatidylinositol 3-Kinase-dependent Activation of Protein Kinase C-ζ in Bacterial Lipopolysaccharide-treated Human Monocytes* , 1997, The Journal of Biological Chemistry.

[49]  A. Puls,et al.  Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[50]  M. Diaz-Meco,et al.  The Product of par-4, a Gene Induced during Apoptosis, Interacts Selectively with the Atypical Isoforms of Protein Kinase C , 1996, Cell.

[51]  P. Parker,et al.  Phosphorylation of threonine 638 critically controls the dephosphorylation and inactivation of protein kinase Cα , 1996, Current Biology.

[52]  Sabina Hrabetova,et al.  Bidirectional Regulation of Protein Kinase Mζ in the Maintenance of Long-Term Potentiation and Long-Term Depression , 1996, The Journal of Neuroscience.

[53]  J. Strominger,et al.  Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[54]  S. Moriya,et al.  EGF or PDGF receptors activate atypical PKClambda through phosphatidylinositol 3‐kinase. , 1996, The EMBO journal.

[55]  M. Diaz-Meco,et al.  Evidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta. , 1995, The EMBO journal.

[56]  D. Fabbro,et al.  PKC zeta is a molecular switch in signal transduction of TNF‐alpha, bifunctionally regulated by ceramide and arachidonic acid. , 1995, The EMBO journal.

[57]  C. Limatola,et al.  Phosphatidic acid activation of protein kinase C-zeta overexpressed in COS cells: comparison with other protein kinase C isotypes and other acidic lipids. , 1994, The Biochemical journal.

[58]  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. , 1994, The Journal of biological chemistry.

[59]  W. Fair,et al.  Differential expression of protein kinase C isozyme messenger RNAs in dunning R-3327 rat prostatic tumors. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[60]  C. Schmitz‐Peiffer,et al.  Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells. , 1993, The Journal of biological chemistry.

[61]  T. Sacktor,et al.  Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[62]  J. Exton,et al.  Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. , 1993, The Journal of biological chemistry.

[63]  P. Parker,et al.  Effect of phorbol esters on protein kinase C-zeta. , 1992, The Journal of biological chemistry.

[64]  Y. Nishizuka,et al.  Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Y. Nishizuka,et al.  The structure, expression, and properties of additional members of the protein kinase C family. , 1988, The Journal of biological chemistry.

[66]  Jaekyoon Shin,et al.  p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition. , 2002, FEBS letters.

[67]  C. Ponting,et al.  OPR, PC and AID: all in the PB1 family. , 2002, Trends in biochemical sciences.

[68]  A. Durán,et al.  Targeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway. , 2001, Molecular cell.

[69]  M. Kazanietz,et al.  Atypical Protein Kinase C-ζ Stimulates Thyrotropin-Independent Proliferation in Rat Thyroid Cells1. , 2000, Endocrinology.

[70]  C. Marshall,et al.  Activation of the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway by Conventional, Novel, and Atypical Protein Kinase C Isotypes , 1998 .

[71]  J. Avruch,et al.  Atypical protein kinase C k binds and regulates p70 S6 kinase , 1998 .

[72]  Lairdbloom Andh . Roberthorvitz.  The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation , 1997 .