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Journal of Cell Science, Vol 113, Issue 10 1671-1676, Copyright © 2000 by Company of Biologists

JOURNAL ARTICLES

Rising behind NO: cGMP-dependent protein kinases

F Hofmann, A Ammendola and J Schlossmann
Institut fur Pharmakologie und Toxikologie, TU Munchen, Biedersteiner Str. 29, D-80802 Munchen, Germany. hofmann@ipt.med. tu-muenchen.de.

Over the past few years, a wealth of biochemical and functional data has been gathered on mammalian cGMP-dependent protein kinases (cGKs). In mammals, three different kinases are encoded by two genes. Mutant and chimeric cGMP kinase proteins generated by molecular biology techniques have yielded important biochemical knowledge, such as the function of the N-terminal domains of cGKI and cGKII, the identity of the cGMP-binding sites of cGKI, the substrate specificity of the enzymes and structural details of the catalytic center. Genetic approaches have proved to be especially useful for the analysis of the biological function of cGKs. Recently, some of the in vivo targets and mechanisms leading to smooth muscle relaxation have been identified. In vivo targets are the myosin-binding subunit of myosin phosphatase (PP1M), a member of the protein phosphatase 1, the calcium-activated maxi K(+) channel and a new protein named IRAG that forms a complex with the inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) receptor and cGKI. Phosphorylation of PP1M by cGKI(alpha) activates myosin phosphatase, whereas phosphorylation of IRAG by cGKI(beta) decreases Ins(1,4, 5)P(3)-induced calcium release. cGKII regulates in vivo intestinal fluid secretion by phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR), bone growth and renal renin secretion by phosphorylation of unknown proteins.
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P. Sinnaeve, J.-D. Chiche, H. Gillijns, N. Van Pelt, D. Wirthlin, F. Van de Werf, D. Collen, K. D. Bloch, and S. Janssens
Overexpression of a Constitutively Active Protein Kinase G Mutant Reduces Neointima Formation and In-Stent Restenosis
Circulation, June 18, 2002; 105(24): 2911 - 2916.
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 Circ. Res.Home page
R. Feil, N. Gappa, M. Rutz, J. Schlossmann, C. R. Rose, A. Konnerth, S. Brummer, S. Kuhbandner, and F. Hofmann
Functional Reconstitution of Vascular Smooth Muscle Cells With cGMP-Dependent Protein Kinase I Isoforms
Circ. Res., May 31, 2002; 90(10): 1080 - 1086.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. M. Gurnett, P. A. Liberator, P. M. Dulski, S. P. Salowe, R. G. K. Donald, J. W. Anderson, J. Wiltsie, C. A. Diaz, G. Harris, B. Chang, et al.
Purification and Molecular Characterization of cGMP-dependent Protein Kinase from Apicomplexan Parasites. A NOVEL CHEMOTHERAPEUTIC TARGET
J. Biol. Chem., May 3, 2002; 277(18): 15913 - 15922.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
H. Mollnau, M. Wendt, K. Szocs, B. Lassegue, E. Schulz, M. Oelze, H. Li, M. Bodenschatz, M. August, A. L. Kleschyov, et al.
Effects of Angiotensin II Infusion on the Expression and Function of NAD(P)H Oxidase and Components of Nitric Oxide/cGMP Signaling
Circ. Res., March 8, 2002; 90 (4): e58 - e65.
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 Circ. Res.Home page
H. Sellak, X. Yang, X. Cao, T. Cornwell, G. A. Soff, and T. Lincoln
Sp1 Transcription Factor as a Molecular Target for Nitric Oxide- and Cyclic Nucleotide-Mediated Suppression of cGMP-Dependent Protein Kinase-I{alpha} Expression in Vascular Smooth Muscle Cells
Circ. Res., March 8, 2002; 90(4): 405 - 412.
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 Mol. Pharmacol.Home page
C. Ibarra-Alvarado, J. Galle, V. O. Melichar, A. Mameghani, and H. H. H. W. Schmidt
Phosphorylation of Blood Vessel Vasodilator-Stimulated Phosphoprotein at Serine 239 as a Functional Biochemical Marker of Endothelial Nitric Oxide/Cyclic GMP Signaling
Mol. Pharmacol., February 1, 2002; 61(2): 312 - 319.
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 J. Biol. Chem.Home page
M.-P. Gratacap, B. Payrastre, B. Nieswandt, and S. Offermanns
Differential Regulation of Rho and Rac through Heterotrimeric G-proteins and Cyclic Nucleotides
J. Biol. Chem., December 14, 2001; 276(51): 47906 - 47913.
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 Am. J. Physiol. Cell Physiol.Home page
K. D. Keef, J. R. Hume, and J. Zhong
Regulation of cardiac and smooth muscle Ca2+ channels (CaV1.2a,b) by protein kinases
Am J Physiol Cell Physiol, December 1, 2001; 281(6): C1743 - C1756.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
T. M. Lincoln, N. Dey, and H. Sellak
Signal Transduction in Smooth Muscle: Invited Review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression
J Appl Physiol, September 1, 2001; 91(3): 1421 - 1430.
[Abstract] [Full Text] [PDF]

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 J Biomol ScreenHome page
B. Bader, E. Butt, A. Palmetshofer, U. Walter, T. Jarchau, and P. Drueckesl
A cGMP-Dependent Protein Kinase Assay for High Throughput Screening Based on Time-Resolved Fluorescence Resonance Energy Transfer
J Biomol Screen, August 1, 2001; 6(4): 255 - 264.
[Abstract] [PDF]

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 Circ. Res.Home page
M. Oelze, H. Mollnau, N. Hoffmann, A. Warnholtz, M. Bodenschatz, A. Smolenski, U. Walter, M. Skatchkov, T. Meinertz, and T. Munzel
Vasodilator-Stimulated Phosphoprotein Serine 239 Phosphorylation as a Sensitive Monitor of Defective Nitric Oxide/cGMP Signaling and Endothelial Dysfunction
Circ. Res., November 24, 2000; 87(11): 999 - 1005.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
M. Sausbier, R. Schubert, V. Voigt, C. Hirneiss, A. Pfeifer, M. Korth, T. Kleppisch, P. Ruth, and F. Hofmann
Mechanisms of NO/cGMP-Dependent Vasorelaxation
Circ. Res., October 27, 2000; 87(9): 825 - 830.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
C. Xia, Z. Bao, C. Yue, B. M. Sanborn, and M. Liu
Phosphorylation and Regulation of G-protein-activated Phospholipase C-beta 3 by cGMP-dependent Protein Kinases
J. Biol. Chem., June 1, 2001; 276(23): 19770 - 19777.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D. D. Browning, M. Mc Shane, C. Marty, and R. D. Ye
Functional Analysis of Type 1alpha cGMP-dependent Protein Kinase Using Green Fluorescent Fusion Proteins
J. Biol. Chem., April 13, 2001; 276(16): 13039 - 13048.
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 J. Biol. Chem.Home page
E. Butt, D. Immler, H. E. Meyer, A. Kotlyarov, K. Laa{beta}, and M. Gaestel
Heat Shock Protein 27 Is a Substrate of cGMP-dependent Protein Kinase in Intact Human Platelets. PHOSPHORYLATION-INDUCED ACTIN POLYMERIZATION CAUSED BY HSP27 MUTANTS
J. Biol. Chem., March 2, 2001; 276(10): 7108 - 7113.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Ammendola, A. Geiselhoringer, F. Hofmann, and J. Schlossmann
Molecular Determinants of the Interaction between the Inositol 1,4,5-Trisphosphate Receptor-associated cGMP Kinase Substrate (IRAG) and cGMP Kinase Ibeta
J. Biol. Chem., June 22, 2001; 276(26): 24153 - 24159.
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 J. Biol. Chem.Home page
M. Di Fulvio, P. K. Lauf, and N. C. Adragna
Nitric Oxide Signaling Pathway Regulates Potassium Chloride Cotransporter-1 mRNA Expression in Vascular Smooth Muscle Cells
J. Biol. Chem., November 21, 2001; 276(48): 44534 - 44540.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. J. Khatri, K. M. Joyce, F. V. Brozovich, and S. A. Fisher
Role of Myosin Phosphatase Isoforms in cGMP-mediated Smooth Muscle Relaxation
J. Biol. Chem., September 28, 2001; 276(40): 37250 - 37257.
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 JCBHome page
F. Mullershausen, M. Russwurm, W. J. Thompson, L. Liu, D. Koesling, and A. Friebe
Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5 paralleled by phosphorylation of the enzyme
J. Cell Biol., October 15, 2001; 155(2): 271 - 278.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
H. Sellak, X. Yang, X. Cao, T. Cornwell, G. A. Soff, and T. Lincoln
Sp1 Transcription Factor as a Molecular Target for Nitric Oxide- and Cyclic Nucleotide-Mediated Suppression of cGMP-Dependent Protein Kinase-I{alpha} Expression in Vascular Smooth Muscle Cells
Circ. Res., March 8, 2002; 90(4): 405 - 412.
[Abstract] [Full Text] [PDF]


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