6bys

From Proteopedia

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Revision as of 07:27, 23 May 2019

Structures of the PKA RI alpha holoenzyme with the FLHCC driver J-PKAc alpha or native PRKAc alpha

Structural highlights

6bys is a 8 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	,
Gene:	PRKACA, PKACA (HUMAN), PRKAR1A (BOVIN)
Activity:	cAMP-dependent protein kinase, with EC number 2.7.11.11
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KAPCA_HUMAN] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3G and AICDA.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] [KAP0_BOVIN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

Publication Abstract from PubMed

Fibrolamellar hepatocellular carcinoma (FLHCC) is driven by J-PKAcalpha, a kinase fusion chimera of the J domain of DnaJB1 with PKAcalpha, the catalytic subunit of protein kinase A (PKA). Here we report the crystal structures of the chimeric fusion RIalpha2:J-PKAcalpha2 holoenzyme formed by J-PKAcalpha and the PKA regulatory (R) subunit RIalpha, and the wild-type (WT) RIalpha2:PKAcalpha2 holoenzyme. The chimeric and WT RIalpha holoenzymes have quaternary structures different from the previously solved WT RIbeta and RIIbeta holoenzymes. The WT RIalpha holoenzyme showed the same configuration as the chimeric RIalpha2:J-PKAcalpha2 holoenzyme and a distinct second conformation. The J domains are positioned away from the symmetrical interface between the two RIalpha:J-PKAcalpha heterodimers in the chimeric fusion holoenzyme and are highly dynamic. The structural and dynamic features of these holoenzymes enhance our understanding of the fusion chimera protein J-PKAcalpha that drives FLHCC as well as the isoform specificity of PKA.

Structures of the PKA RIalpha Holoenzyme with the FLHCC Driver J-PKAcalpha or Wild-Type PKAcalpha.,Cao B, Lu TW, Martinez Fiesco JA, Tomasini M, Fan L, Simon SM, Taylor SS, Zhang P Structure. 2019 Mar 15. pii: S0969-2126(19)30079-6. doi:, 10.1016/j.str.2019.03.001. PMID:30905674^[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ahmmed GU, Mehta D, Vogel S, Holinstat M, Paria BC, Tiruppathi C, Malik AB. Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells. J Biol Chem. 2004 May 14;279(20):20941-9. Epub 2004 Mar 10. PMID:15016832 doi:10.1074/jbc.M313975200
↑ Guan H, Hou S, Ricciardi RP. DNA binding of repressor nuclear factor-kappaB p50/p50 depends on phosphorylation of Ser337 by the protein kinase A catalytic subunit. J Biol Chem. 2005 Mar 18;280(11):9957-62. Epub 2005 Jan 7. PMID:15642694 doi:10.1074/jbc.M412180200
↑ D'Souza T, Agarwal R, Morin PJ. Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells. J Biol Chem. 2005 Jul 15;280(28):26233-40. Epub 2005 May 19. PMID:15905176 doi:10.1074/jbc.M502003200
↑ Zhang F, Hu Y, Huang P, Toleman CA, Paterson AJ, Kudlow JE. Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. J Biol Chem. 2007 Aug 3;282(31):22460-71. Epub 2007 Jun 12. PMID:17565987 doi:10.1074/jbc.M702439200
↑ Xiao B, Tian X, Xie W, Jones PP, Cai S, Wang X, Jiang D, Kong H, Zhang L, Chen K, Walsh MP, Cheng H, Chen SR. Functional consequence of protein kinase A-dependent phosphorylation of the cardiac ryanodine receptor: sensitization of store overload-induced Ca2+ release. J Biol Chem. 2007 Oct 12;282(41):30256-64. Epub 2007 Aug 10. PMID:17693412 doi:10.1074/jbc.M703510200
↑ Xu H, Washington S, Verderame MF, Manni A. Activation of protein kinase A (PKA) signaling mitigates the antiproliferative and antiinvasive effects of alpha-difluoromethylornithine in breast cancer cells. Breast Cancer Res Treat. 2008 Jan;107(1):63-70. Epub 2007 Feb 27. PMID:17333334 doi:10.1007/s10549-007-9536-5
↑ Gambaryan S, Kobsar A, Rukoyatkina N, Herterich S, Geiger J, Smolenski A, Lohmann SM, Walter U. Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex. J Biol Chem. 2010 Jun 11;285(24):18352-63. doi: 10.1074/jbc.M109.077602. Epub, 2010 Mar 31. PMID:20356841 doi:10.1074/jbc.M109.077602
↑ Wang W, Zhang X, Zheng J, Yang J. High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP/protein kinase A/extracellular signal-regulated kinase pathway. Mol Cell Biochem. 2010 May;338(1-2):115-22. doi: 10.1007/s11010-009-0344-6. Epub , 2009 Dec 1. PMID:19949837 doi:10.1007/s11010-009-0344-6
↑ Ermisch M, Firla B, Steinhilber D. Protein kinase A activates and phosphorylates RORalpha4 in vitro and takes part in RORalpha activation by CaMK-IV. Biochem Biophys Res Commun. 2011 May 13;408(3):442-6. doi:, 10.1016/j.bbrc.2011.04.046. Epub 2011 Apr 13. PMID:21514275 doi:10.1016/j.bbrc.2011.04.046
↑ Vetter MM, Zenn HM, Mendez E, van den Boom H, Herberg FW, Skalhegg BS. The testis-specific Calpha2 subunit of PKA is kinetically indistinguishable from the common Calpha1 subunit of PKA. BMC Biochem. 2011 Aug 3;12:40. doi: 10.1186/1471-2091-12-40. PMID:21812984 doi:10.1186/1471-2091-12-40
↑ Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nistico R, Scorziello A, Savoia C, Garbi C, Annunziato L, Feliciello A. Control of PKA stability and signalling by the RING ligase praja2. Nat Cell Biol. 2011 Apr;13(4):412-22. doi: 10.1038/ncb2209. Epub 2011 Mar 20. PMID:21423175 doi:10.1038/ncb2209
↑ Cao B, Lu TW, Martinez Fiesco JA, Tomasini M, Fan L, Simon SM, Taylor SS, Zhang P. Structures of the PKA RIalpha Holoenzyme with the FLHCC Driver J-PKAcalpha or Wild-Type PKAcalpha. Structure. 2019 Mar 15. pii: S0969-2126(19)30079-6. doi:, 10.1016/j.str.2019.03.001. PMID:30905674 doi:http://dx.doi.org/10.1016/j.str.2019.03.001

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6bys"

@@ Line 3: / Line 3: @@
 <StructureSection load='6bys' size='340' side='right'caption='[[6bys]], [[Resolution|resolution]] 4.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6bys]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BYS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6bys]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BYS FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKACA, PKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRKAR1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bys OCA], [http://pdbe.org/6bys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bys RCSB], [http://www.ebi.ac.uk/pdbsum/6bys PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bys ProSAT]</span></td></tr>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 6bys" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Bovin]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: CAMP-dependent protein kinase]]

6bys

From Proteopedia

Revision as of 07:27, 23 May 2019

Structures of the PKA RI alpha holoenzyme with the FLHCC driver J-PKAc alpha or native PRKAc alpha

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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