Insulin-Stimulated Cyclic Guanosine Monophosphate Inhibits Vascular Smooth Muscle Cell Migration by Inhibiting Ca/Calmodulin-Dependent Protein Kinase II

Zhang, Sui; Yang, Yonggong; Kone, Bruce C.; Allen, Julius C.; Kahn, Andrew

doi:10.1161/01.cir.0000056766.45109.c1

Cited by 32 publications

(33 citation statements)

References 43 publications

(46 reference statements)

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“…Insulin has been shown to inhibit, to have no effect, and to stimulate cultured VSMC migration depending on the experimental conditions (9)(10)(11)(12)(13). The present study has demonstrated that insulin can induce a low level of migration in human coronary smooth muscle cells in two distinct assays.…”

Section: Discussionmentioning

confidence: 51%

Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent

Roztocil

Nicholl

2008

Surgery

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Background-With the rise in metabolic syndrome, understanding the role of insulin signaling within the cells of vasculature has become more important but yet remains poorly defined. The study examines the role of insulin actions on a pivotal cross-talk receptor, Epidermal Growth Factor Receptor (EGFR). EGFR is transactivated by both G-protein-coupled receptors and receptor linked tyrosine kinases and is key to many of their responses.

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Section: Discussionmentioning

confidence: 51%

Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent

Roztocil

Nicholl

2008

Surgery

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“…Yet, the mechanisms underlying PKG-dependent increase in migration of immune cells are unknown. In smooth muscle and endothelial cells, PKG signaling has been reported to both stimulate and inhibit motility (Brown et al, 1999;Dubey et al, 1995;Kawasaki et al, 2003;Rolli-Derkinderen et al, 2010;Smolenski et al, 2000;Zhang et al, 2003); these conflicting results may be explained by differences in primary cell cultures and/or variations in cell migration assays. While the inhibitory effects are mediated, at least partly, through PKG phosphorylation of VASP or induction of MAP kinase phosphatase-1 (Jacob et al, 2002;Smolenski et al, 2000), pro-migratory effects of PKG depend on activation of phosphatidylinositol 3-kinase and RhoA phosphorylation (Kawasaki et al, 2003;Rolli-Derkinderen et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

cGMP-dependent Protein Kinase Iβ Regulates Breast Cancer Cell Migration and Invasion via a Novel Interaction with the Actin/Myosin-associated Protein Caldesmon

Schwappacher

Rangaswami

Su-Yuo

et al. 2013

Journal of Cell Science

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SummaryThe two isoforms of type I cGMP-dependent protein kinase (PKGIa and PKGIb) differ in their first ,100 amino acids, giving each isoform unique dimerization and autoinhibitory domains. The dimerization domains form coiled-coil structures and serve as platforms for isoform-specific protein-protein interactions. Using the PKGIb dimerization domain as an affinity probe in a proteomic screen, we identified the actin/myosin-associated protein caldesmon (CaD) as a PKGIb-specific binding protein. PKGIb phosphorylated human CaD on serine 12 in vitro and in intact cells. Phosphorylation on serine 12 or mutation of serine 12 to glutamic acid (S12E) reduced the interaction between CaD and myosin IIA. Because CaD inhibits myosin ATPase activity and regulates cell motility, we examined the effects of PKGIb and CaD on cell migration and invasion. Inhibition of the NO/cGMP/PKG pathway reduced migration and invasion of human breast cancer cells, whereas PKG activation enhanced their motility and invasion. siRNA-mediated knockdown of endogenous CaD had pro-migratory and pro-invasive effects in human breast cancer cells. Reconstituting cells with wild-type CaD slowed migration and invasion; however, CaD containing a phospho-mimetic S12E mutation failed to reverse the pro-migratory and pro-invasive activity of CaD depletion. Our data suggest that PKGIb enhances breast cancer cell motility and invasive capacity, at least in part, by phosphorylating CaD. These findings identify a pro-migratory and pro-invasive function for PKGIb in human breast cancer cells, suggesting that PKGIb is a potential target for breast cancer treatment.

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“…19 Moreover, cGMP was recently proposed to be involved in other signaling pathways including MAPK1 20 and CaMKinase II cascade. 21 In addition, while recent analysis of the promoter region of murine Npr1 has revealed the presence of several binding sites for a variety of nuclear factors, including HFH-3, CREB, SRY, and USF, 14 no known transcription factors matched the cGMP-RE sequence, 15 suggesting that this is a novel cisacting element. Although the element described here was identified in the promoter regions of mouse, rat, and human Npr1, our search did not detect an identical element in the promoters of other cGMP-regulated genes, suggesting a specific mode of regulation for Npr1.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a cGMP-Response Element in the Guanylyl Cyclase/Natriuretic Peptide Receptor A Gene Promoter

et al. 2004

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Abstract-Previous studies have shown that atrial natriuretic peptide (ANP) can inhibit transcription of its receptor, guanylyl cyclase A, by a mechanism dependent on cGMP and have suggested the presence of a putative cGMP-response element (cGMP-RE) in the Npr1 gene promoter. To localize and characterize the putative cis-acting element, we have subcloned a 1520-bp fragment of the rat Npr1 promoter in an expression vector containing the luciferase reporter gene. Several fragments, generated by exonuclease III-directed deletions, were transiently transfected into cells to measure their promoter activity. Deletion from Ϫ1520 to Ϫ1396 of a 1520-bp-long Npr1 promoter led to a 5-fold increase in luciferase activity. Subsequent deletion to the position Ϫ1307 resulted in a decrease of luciferase activity by 90%. Preincubation of cells with 100 nM of ANP or 100 M 8-bromo-cGMP inhibited luciferase activity of the 1520-bp and 1396-bp-long fragments, but not the activity of the 1307-bp fragment, suggesting that the cGMP-RE is localized between positions Ϫ1396 and Ϫ1307. The cGMP regulatory region was narrowed by gel shift assays and footprinting to position Ϫ1372 to Ϫ1354 from the transcription start site of Npr1 and indicated its interaction with transcriptional factor(s). Cross-competition experiments with mutated oligonucleotides led to the definition of a consensus sequence (Ϫ1372 AaAtRKaNTTCaAcAKTY Ϫ1354) for the novel cGMP-RE, which is conserved in the human (75% identity) and mouse (95% identity) Npr1 promoters. Key Words: cyclic GMP Ⅲ natriuretic peptides Ⅲ receptors, atrial natriuretic factor A trial natriuretic peptide (ANP) is a cardiac hormone with potent effects in the kidney, vasculature, and nervous system. It has vasorelaxant activity in vascular smooth muscle and promotes urinary sodium and water excretion by the kidney (for review, see Reference 1 ). These actions of ANP are brought about via the activation of membrane-bound protein, natriuretic peptide receptor type A (NPR-A), or guanylyl cyclase A. 2-4 NPR-A is a 130-KDa transmembrane protein containing an ANP-binding motif at its extracellular NH 2 terminus and GC activity at its COOH-terminal intracellular domain. 5 Activation of NPR-A leads to the conversion of GTP to the intracellular second messenger cGMP, which is involved in most of the biological responses associated with natriuretic peptides. 2-5 Increased cGMP yields receptor desensitization, resulting in a decrease of ANP-stimulated cGMP synthesis. 6 Receptor preoccupancy appears to be a mechanism of apparent receptor desensitization 7 but transfection experiments with NPR-A cDNA have revealed that early desensitization by ANP pretreatment can be due to dephosphorylation of NPR-A protein. 8 Besides, a previous study demonstrated that NPR-A activity, as well as its mRNA levels, is diminished in a time-and concentration-dependent manner by ANP or by a cell-permeable cGMP analog, 8-bromo-cGMP. 9 Those results suggest transcriptional regulation via a putative cGMPresponse element (cGMP-RE) in the p...

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Insulin-Stimulated Cyclic Guanosine Monophosphate Inhibits Vascular Smooth Muscle Cell Migration by Inhibiting Ca/Calmodulin-Dependent Protein Kinase II

Cited by 32 publications

References 43 publications

Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent

Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent

cGMP-dependent Protein Kinase Iβ Regulates Breast Cancer Cell Migration and Invasion via a Novel Interaction with the Actin/Myosin-associated Protein Caldesmon

Characterization of a cGMP-Response Element in the Guanylyl Cyclase/Natriuretic Peptide Receptor A Gene Promoter

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