Protein kinase C

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{{STRUCTURE_3gpe| PDB=3gpe | SIZE=400| SCENE= |right|CAPTION=Rat protein kinase a C2 domain complex with phosphatidylinositol, phosphate and Ca+2 ion (green), [[3gpe]] }}
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<StructureSection load='' size='350' side='right' caption='Rat protein kinase α C2 domain complex with phosphatidylinositol, phosphate and Ca+2 ion (green), [[3gpe]] ' scene='46/468129/Cv/1'>
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__TOC__
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== Function ==
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'''Protein kinase C''' (PKC) phosphorylates serine or threonine residues in proteins. PKC act in signal transduction pathways<ref>PMID:11440359</ref>. PKC consists of regulatory domain hinged to a catalytic domain. The regulatory domain contains the C1 region which binds diacylglycerol (DAG) and phorbol esters and the C2 domain which is a Ca+2 sensor. PKC contains Pleckstrin Homology (PH) domain which binds phosphatidylinositol lipids (PTDINS). The PH domain is found in proteins involved in intracellular signaling.
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'''Protein kinase C''' (PKC) phosphorylate serine or threonine residues in proteins. They act in signal transduction pathways. Conventional PKC (CPKC) - α, β1, β2, γ – are activated by diacylglycerol (DAG), Ca+2 and a phospholipid. Novel PKC (NPKC) – δ, ε, η, θ – are activated by DAG. Atypical (APKC) do not require DAG or Ca+2 for activation. PKC consists of regulatory domain hinged to a catalytic domain. The regulatory domain contains the C1 region which binds DAG and phorbol esters and the C2 domain which is a Ca+2 sensor. PKC contains Pleckstrin Homology (PH) domain which binds phosphatidylinositol lipids (PTDINS). The PH domain is found in proteins involved in intracellular signaling.
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*'''Conventional PKC''' (CPKC) - α, β1, β2, γ – are activated by DAG, Ca+2 and a phospholipid.<br />
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*'''Novel PKC''' (NPKC) – δ, ε, η, θ – are activated by DAG.<br />
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*'''Atypical PKC''' (APKC) do not require DAG or Ca+2 for activation.
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==3D structures of protein kinase C==
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== Relevance ==
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Activation of PKC and elevated levels of DAG are associated with vascular abnormalities in retinal, renal and cardiovascular tissues. Inhibitors of PKC-β are tested for prevention of diabetic complications<ref>PMID:9604860</ref>. Activation of PKC-α and PKC-β are linked to malignant phenotypes while PKC-δ is thought to mediate anti-cancer effects<ref>PMID:15907369</ref>.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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== Structural highlights ==
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<scene name='46/468129/Cv/6'>Phosphatidylinositol binds to PKC-α C2 domain groove</scene> near the <scene name='46/468129/Cv/7'>Ca+2 binding pocket</scene><ref>PMID:19346474</ref>. Water molecules are shown as red spheres.
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==Conventional PKCs==
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==3D structures of protein kinase C==
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[[Protein kinase C 3D structures]]
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===PKC-a===
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[[1dsy]], [[3rdj]], [[3twy]] – rCPKC-α C2 domain – rat
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[[3rdl]], [[4l1l]] - rCPKC-α C2 domain + ion
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[[3gpe]] - rCPKC-α C2 domain + Ca + PTDINS
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[[2eli]] – hCPKC-α C1 domain – human – NMR<br />
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[[4dnl]] - hCPKC-α C2 domain<br />
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[[3iw4]] - hCPKC-α kinase domain + inhibitor
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===PKC-β===
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[[1a25]] – rCPKC-β C2 domain
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===PKC-β2===
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[[2i0e]] - hCPKC-β2 catalytic domain
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[[3pfq]] - rCPKC-β2 (mutant)
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===PKC-γ===
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[[2uzp]] - hCPKC-γ C2 domain
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[[2e73]] - hCPKC-γ C1 domain - NMR
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[[1tbn]], [[1tbo]] - rCPKC-γ C2 domain – NMR
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==Novel PKC==
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===PKC-δ===
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[[1ptq]] – mNPKC-δ C2 domain – mouse<br />
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[[3uej]] - mNPKC-δ C1B domain<br />
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[[3uey]], [[3uff]], [[3ugd]], [[3ugi]], [[3ugl]] - mNPKC-δ C1B domain (mutant)<br />
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[[1ptr]] - mNPKC-δ C2 domain + phorbol-acetate
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[[1bdy]] - rNPKC-δ C2 domain
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[[1yrk]] – hNPKC-δ C2 domain + peptide
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[[2yuu]] - hNPKC-δ C1 domain - NMR
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[[2coa]] - hNPKC-δ PH domain – NMR
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===PKC-ε===
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[[1gmi]] – rNPKC-ε C2 domain
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===PKC-τ===
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[[2enj]] - hNPKC-τ C2 domain – NMR
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[[2enn]], [[2enz]] - hNPKC-τ C1 domain – NMR
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[[1xjd]] – hNPKC-τ + saurosporine
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[[2jed]] - hNPKC-τ kinase domain + inhibitor
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===PKC-η===
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[[2fk9]] – hNPKC-η C2 domain<br />
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[[3txo]] - hNPKC-η kinase domain (mutant) + inhibitor<br />
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===PKC-θ===
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[[4fkd]] – hNPKC-θ second Cys-rich regulatory domain<br />
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==Atypical PKC==
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===PKC-ι===
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[[1vd2]] – hAPKC-ι PB1 domain – NMR
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[[1zrz]] - hAPKC-ι catalytic domain
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[[3a8w]], [[3a8x]] - hAPKC-ι kinase domain<br />
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[[3zh8]] - hAPKC-ι kinase domain (mutant) + inhibitor<br />
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[[1wmh]] - hAPKC-ι PB1 domain + PAR6 alpha<br />
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[[4dc2]] - hAPKC-ι residues 231-595 + PAR3 peptide<br />
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===PKC-ν===
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[[2d9z]] – hPKC-ν PH domain - NMR
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</StructureSection>
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Rat protein kinase α C2 domain complex with phosphatidylinositol, phosphate and Ca+2 ion (green), 3gpe

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References

  1. ↑ Idris I, Gray S, Donnelly R. Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes. Diabetologia. 2001 Jun;44(6):659-73. PMID:11440359 doi:http://dx.doi.org/10.1007/s001250051675
  2. ↑ Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes. 1998 Jun;47(6):859-66. PMID:9604860
  3. ↑ Koivunen J, Aaltonen V, Peltonen J. Protein kinase C (PKC) family in cancer progression. Cancer Lett. 2006 Apr 8;235(1):1-10. PMID:15907369 doi:http://dx.doi.org/10.1016/j.canlet.2005.03.033
  4. ↑ Guerrero-Valero M, Ferrer-Orta C, Querol-Audi J, Marin-Vicente C, Fita I, Gomez-Fernandez JC, Verdaguer N, Corbalan-Garcia S. Structural and mechanistic insights into the association of PKC{alpha}-C2 domain to PtdIns(4,5)P2. Proc Natl Acad Sci U S A. 2009 Apr 3. PMID:19346474

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