Signal transduction by cGMP-dependent protein kinases and their emerging roles in the regulation of cell adhesion and gene expression

Eigenthaler, Martin; Lohmann, Suzanne M.; Walter, Ulrich; Pilz, Renate B.

doi:10.1007/bfb0033673

Cited by 63 publications

(40 citation statements)

References 143 publications

(167 reference statements)

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“…PKG I has been identified as a critical downstream target of cGMP in this regard. 28 One important cGMP-independent pathway involves the reaction of NO with superoxide to form peroxynitrite. 29 The suppressive effects of SNAP on MLP abundance in ET-1-treated cardiomyocytes were partially reduced by the superoxide scavenger SOD (Figure 2A) and by the SOD mimetic MnTBAP (not shown), indicating that superoxide is involved in the inhibitory effects of NO.…”

Section: No Downregulates Mlp By Cgmp-dependent and Superoxide/peroxymentioning

confidence: 99%

Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide

et al. 2003

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Background-In chronic heart failure, myocardial expression of the inducible isoform of nitric oxide (NO) synthase (NOS2) is enhanced, leading to a sustained production of NO. We postulated that NO modulates expression of genes in cardiac myocytes that may be functionally important in the context of cardiac hypertrophy and failure. Methods and Results-As revealed by cDNA expression array analyses, the NO donor SNAP, which has been shown previously to inhibit agonist-induced cardiac myocyte hypertrophy, downregulates expression of the cytoskeletonassociated muscle LIM protein (MLP) in endothelin-1 (ET-1)-stimulated neonatal rat cardiac myocytes. Northern blotting and immunoblotting experiments confirmed this finding and established that SNAP negatively controls MLP mRNA (Ϫ49%, PϽ0.01) and protein (Ϫ52%, PϽ0.01) abundance in ET-1-treated cardiomyocytes via cGMPdependent protein kinase and superoxide/peroxynitrite-dependent signaling pathways. Treatment of cardiac myocytes with IL-1␤ and IFN-␥ downregulated MLP expression levels via induction of NOS2. Moreover, expression levels of NOS2 and MLP were inversely correlated in the failing human heart, indicating that NOS2 may regulate MLP abundance in vitro and in vivo. Antisense oligonucleotides were used to explore the functional consequences of reduced MLP expression levels in cardiac myocytes. Like SNAP, antisense downregulation of MLP protein expression (Ϫ52%, PϽ0.01) blunted the increases in protein synthesis, cell size, and sarcomere organization in response to ET-1 stimulation. Conversely, overexpression of MLP augmented cell size and sarcomere organization in cardiac myocytes. Conclusions-NO negatively controls MLP expression in cardiac myocytes. Because MLP is necessary and sufficient for hypertrophy and sarcomere assembly, MLP downregulation may restrain hypertrophic growth in pathophysiological situations with increased cardiac NO production.

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Section: No Downregulates Mlp By Cgmp-dependent and Superoxide/peroxymentioning

confidence: 99%

Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide

et al. 2003

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“…The nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (G-kinase) signal transduction pathway is important for regulation of cell growth, differentiation, and apoptosis (43). There are two major types of G-kinase: a soluble type I and a membrane-bound type II.…”

Section: Role Of Tfii-i In G-kinase Pathwaymentioning

confidence: 99%

“…There are two major types of G-kinase: a soluble type I and a membrane-bound type II. While type I G-kinase is widely expressed and present in smooth muscle and endothelial and neuronal cells, type II G-kinase is more limited in expression (43). The G-kinase signaling pathway regulates gene expression in various cell types, both at the transcriptional as well at the posttranscriptional level.…”

Section: Role Of Tfii-i In G-kinase Pathwaymentioning

confidence: 99%

“…The G-kinase signaling pathway regulates gene expression in various cell types, both at the transcriptional as well at the posttranscriptional level. The resulting transcriptional effects are either positive or negative (43). For example, transcriptional regulation of c-fos by nitric oxide and cGMP can occur by nuclear translocation of G-kinase I (43,44).…”

Section: Role Of Tfii-i In G-kinase Pathwaymentioning

confidence: 99%

“…The resulting transcriptional effects are either positive or negative (43). For example, transcriptional regulation of c-fos by nitric oxide and cGMP can occur by nuclear translocation of G-kinase I (43,44). Surprisingly, TFII-I was found to specifically interact with G-kinase Iβ in vitro and in vivo (44).…”

Section: Role Of Tfii-i In G-kinase Pathwaymentioning

confidence: 99%

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Signal-induced functions of the transcription factor TFII-I

Roy

2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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We have learned a great deal over the last several years about the molecular mechanisms that govern cell growth, cell division and cell death. Normal cells pass through cell cycle (growth) and divide in response to mitogenic signals that are transduced through their cognate cell surface receptors to the nucleus. Despite the fact that cellular growth and division are mechanistically distinct steps, they are usually coordinately regulated, which is critical for normal cellular proliferation. The precise mechanistic basis for this coordinated regulation is unclear. TFII-I is a unique, signal induced multifunctional transcription factor that is activated upon a variety of signaling pathways and appears to participate in distinct phases of cell growth. For instance, TFII-I is required for growth factorinduced transcriptional activation of the c-fos gene, which is essential for cell cycle entry. Two alternatively spliced isoforms of TFII-I exhibit opposing but necessary functions for mitogen-induced transcriptional activation of c-fos. Besides transcriptional activation of the c-fos proto-oncogene and eventual entry into cell cycle, TFII-I also appears to have a role in later phases of the cell cycle and cell division. Here we discuss how a multitude of signaling inputs target TFII-I isoforms, which may exert their functions in distinct phases of the cell cycle and play a key role in the coordinated regulation of cellular proliferation.

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Cyclic GMP Dependent Protein Kinase ( c GK , PKG )

Smolenski¹,

Lohmann²

2002

Wiley Encyclopedia of Molecular Medicine

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Signal transduction by cGMP-dependent protein kinases and their emerging roles in the regulation of cell adhesion and gene expression

Cited by 63 publications

References 143 publications

Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide

Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide

Signal-induced functions of the transcription factor TFII-I

Cyclic GMP Dependent Protein Kinase ( c GK , PKG )

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