PKG are serine/threonine kinases that are present in a variety of eukaryotes ranging from the unicellular organism Paramecium to humans. Two PKG genes, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified in mammals. The N-terminus of PKG-I is encoded by two alternatively spliced exons that specify for the PKG-Iα and PKG-Iβ isoforms. PKG-Iβ is activated at ~10-fold higher cGMP concentrations than PKG-Iα. The PKG-I and PKG-II are homodimers of two identical subunits (~75 kDa and ~85 kDa, respectively) and share common structural features.
(1) an N-terminal domain that mediates homodimerization, suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates
(2) a regulatory domain that contains two non-identical cGMP-binding sites
(3) a kinase domain that catalyzes the phosphate transfer from ATP to the hydroxyl group of a serine/threonine side chain of the target protein
Binding of cGMP to the regulatory domain induces a conformational change which stops the inhibition of the catalytic core by the N-terminus and allows the phosphorylation of substrate proteins. Whereas PKG-I is predominantly localized in the cytoplasm, PKG-II is anchored to the plasma membrane by N-terminal myristoylation.
Tissue distributionedit
In general, PKG-I and PKG-II are expressed in different cell types.
Cancerous colon cells stop producing PKG, which apparently limits beta-catenin, thus allowing the VEGF enzyme to solicit angiogenesis.[2]
Behavioral genetics in Drosophila melanogasteredit
In Drosophila melanogaster the foraging (for) gene is a polymorphic trait that underlies differences in food-seeking behaviors. The forlocus is made up of Rover (forR) and Sitter (forS) alleles, with the Rover allele being dominant. Rover individuals typically travel greater distances when foraging for food, while Sitter individuals travel less distance to forage for food. Both Rover and Sitter phenotypes are considered wild-type, as fruit fly populations typically exhibit a 70:30 Rover-to-Sitter ratio.[3] The Rover and Sitter alleles are located within the 24A3-5 region of the Drosophila melanogaster polytene chromosome, a region which contains the PKG d2g gene. PKG expression levels account for differences in forR and forS allele frequency and therefore behavior as Rover individuals show higher PKG expression than Sitter individuals, and the Sitter phenotype can be converted to Rover by over-expression of the dg2 gene.[4]
^PDB: 3NMD; Casteel DE, Smith-Nguyen EV, Sankaran B, Roh SH, Pilz RB, Kim C (October 2010). "A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of isoform-specific anchoring". The Journal of Biological Chemistry. 285 (43): 32684–8. doi:10.1074/jbc.C110.161430. PMC2963381. PMID 20826808.
^Kwon IK, Schoenlein PV, Delk J, Liu K, Thangaraju M, Dulin NO, et al. (April 2008). "Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis". Cancer. 112 (7): 1462–70. doi:10.1002/cncr.23334. PMID 18260092. S2CID 4763327.
^Osborne KA, Robichon A, Burgess E, Butland S, Shaw RA, Coulthard A, et al. (August 1997). "Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila". Science. 277 (5327): 834–6. doi:10.1126/science.277.5327.834. PMID 9242616.
cgmp, dependent, protein, kinase, protein, kinase, serine, threonine, specific, protein, kinase, that, activated, cgmp, phosphorylates, number, biologically, important, targets, implicated, regulation, smooth, muscle, relaxation, platelet, function, sperm, met. cGMP dependent protein kinase or protein kinase G PKG is a serine threonine specific protein kinase that is activated by cGMP It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle relaxation platelet function sperm metabolism cell division and nucleic acid synthesis protein kinase cGMP dependent type ICrystallographic structure of the leucine zipper domain of human cGMP dependent protein kinase I beta 1 IdentifiersSymbolPRKG1Alt symbolsPRKGR1B PRKG1BNCBI gene5592HGNC9414OMIM176894RefSeqNM 006258UniProtQ13976Other dataLocusChr 10 q11 2Search forStructuresSwiss modelDomainsInterProprotein kinase cGMP dependent type IIIdentifiersSymbolPRKG2NCBI gene5593HGNC9416OMIM601591RefSeqNM 006259UniProtQ13237Other dataLocusChr 4 q13 1 21 1Search forStructuresSwiss modelDomainsInterPro Contents 1 Genes and proteins 2 Tissue distribution 3 Role in cancer 4 Behavioral genetics in Drosophila melanogaster 5 See also 6 References 7 External linksGenes and proteins editPKG are serine threonine kinases that are present in a variety of eukaryotes ranging from the unicellular organism Paramecium to humans Two PKG genes coding for PKG type I PKG I and type II PKG II have been identified in mammals The N terminus of PKG I is encoded by two alternatively spliced exons that specify for the PKG Ia and PKG Ib isoforms PKG Ib is activated at 10 fold higher cGMP concentrations than PKG Ia The PKG I and PKG II are homodimers of two identical subunits 75 kDa and 85 kDa respectively and share common structural features Each subunit is composed of three functional domains 1 an N terminal domain that mediates homodimerization suppression of the kinase activity in the absence of cGMP and interactions with other proteins including protein substrates 2 a regulatory domain that contains two non identical cGMP binding sites 3 a kinase domain that catalyzes the phosphate transfer from ATP to the hydroxyl group of a serine threonine side chain of the target proteinBinding of cGMP to the regulatory domain induces a conformational change which stops the inhibition of the catalytic core by the N terminus and allows the phosphorylation of substrate proteins Whereas PKG I is predominantly localized in the cytoplasm PKG II is anchored to the plasma membrane by N terminal myristoylation Tissue distribution editIn general PKG I and PKG II are expressed in different cell types PKG I has been detected at high concentrations above 0 1 mmol L in all types of smooth muscle cells SMCs including vascular SMCs and in platelets Lower levels are present in vascular endothelium and cardiomyocytes The enzyme is also expressed in fibroblasts certain types of renal cells and leukocytes and in specific regions of the nervous system for example in the hippocampus in cerebellar Purkinje cells and in dorsal root ganglia Neurons express either the PKG Ia or the PKG Ib isoform platelets predominantly Ib and both isoforms are present in smooth muscle PKG II has been detected in renal cells zona glomerulosa cells of the adrenal cortex club cells in distal airways intestinal mucosa pancreatic ducts parotid and submandibular glands chondrocytes and several brain nuclei but not in cardiac and vascular myocytes Specifically in smooth muscle tissue PKG promotes the opening of calcium activated potassium channels leading to cell hyperpolarization and relaxation and blocks agonist activity of phospholipase C reducing liberation of stored calcium ions by inositol triphosphate Role in cancer editCancerous colon cells stop producing PKG which apparently limits beta catenin thus allowing the VEGF enzyme to solicit angiogenesis 2 Behavioral genetics in Drosophila melanogaster editIn Drosophila melanogaster the foraging for gene is a polymorphic trait that underlies differences in food seeking behaviors The for locus is made up of Rover forR and Sitter forS alleles with the Rover allele being dominant Rover individuals typically travel greater distances when foraging for food while Sitter individuals travel less distance to forage for food Both Rover and Sitter phenotypes are considered wild type as fruit fly populations typically exhibit a 70 30 Rover to Sitter ratio 3 The Rover and Sitter alleles are located within the 24A3 5 region of the Drosophila melanogaster polytene chromosome a region which contains the PKG d2g gene PKG expression levels account for differences in forR and forS allele frequency and therefore behavior as Rover individuals show higher PKG expression than Sitter individuals and the Sitter phenotype can be converted to Rover by over expression of the dg2 gene 4 See also editcAMP dependent protein kinase PKA References edit PDB 3NMD Casteel DE Smith Nguyen EV Sankaran B Roh SH Pilz RB Kim C October 2010 A crystal structure of the cyclic GMP dependent protein kinase I beta dimerization docking domain reveals molecular details of isoform specific anchoring The Journal of Biological Chemistry 285 43 32684 8 doi 10 1074 jbc C110 161430 PMC 2963381 PMID 20826808 Kwon IK Schoenlein PV Delk J Liu K Thangaraju M Dulin NO et al April 2008 Expression of cyclic guanosine monophosphate dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis Cancer 112 7 1462 70 doi 10 1002 cncr 23334 PMID 18260092 S2CID 4763327 Sokolowski MB November 2001 Drosophila genetics meets behaviour Nature Reviews Genetics 2 11 879 90 doi 10 1038 35098592 PMID 11715043 S2CID 13152094 Osborne KA Robichon A Burgess E Butland S Shaw RA Coulthard A et al August 1997 Natural behavior polymorphism due to a cGMP dependent protein kinase of Drosophila Science 277 5327 834 6 doi 10 1126 science 277 5327 834 PMID 9242616 External links editEC 2 7 11 12 Cyclic GMP Dependent Protein Kinases and the Cardiovascular System cGMP Dependent Protein Kinases at the U S National Library of Medicine Medical Subject Headings MeSH Portal nbsp Biology Retrieved from https en wikipedia org w index php title CGMP dependent protein kinase amp oldid 1150932157, wikipedia, wiki, book, books, library,
