Mode-switching of a voltage-gated cation channel is mediated by a protein kinase A-regulated tyrosine phosphatase

Nature ◽  
1993 ◽  
Vol 366 (6454) ◽  
pp. 433-438 ◽  
Author(s):  
Gisela F. Wilson ◽  
Leonard K. Kaczmarek
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Tyrosine Phosphatase ◽  
Cation Channel ◽  
Mode Switching ◽  
Voltage Gated ◽  
Kinase A

scholarly journals Reduction in Voltage-Gated K+ Currents in Primary Cultured Rat Pancreatic β-Cells by Linoleic Acids

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 674-682 ◽  
Author(s):  
Dan Dan Feng ◽  
Ziqiang Luo ◽  
Sang-gun Roh ◽  
Maria Hernandez ◽  
Neveen Tawadros ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Linoleic Acid ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Voltage Gated ◽  
K Current ◽  
K Currents ◽  
Kinase A

Free fatty acids (FFAs), in addition to glucose, have been shown to stimulate insulin release through the G protein-coupled receptor (GPCR)40 receptor in pancreatic β-cells. Intracellular free calcium concentration ([Ca2+]i) in β-cells is elevated by FFAs, although the mechanism underlying the [Ca2+]i increase is still unknown. In this study, we investigated the action of linoleic acid on voltage-gated K+ currents. Nystatin-perforated recordings were performed on identified rat β-cells. In the presence of nifedipine, tetrodotoxin, and tolbutamide, voltage-gated K+ currents were observed. The transient current represents less than 5%, whereas the delayed rectifier current comprises more than 95%, of the total K+ currents. A long-chain unsaturated FFA, linoleic acid (10 μm), reversibly decreased the amplitude of K+ currents (to less than 10%). This reduction was abolished by the cAMP/protein kinase A system inhibitors H89 (1 μm) and Rp-cAMP (10 μm) but was not affected by protein kinase C inhibitor. In addition, forskolin and 8′-bromo-cAMP induced a similar reduction in the K+ current as that evoked by linoleic acid. Insulin secretion and cAMP accumulation in β-cells were also increased by linoleic acid. Methyl linoleate, which has a similar structure to linoleic acid but no binding affinity to GPR40, did not change K+ currents. Treatment of cultured cells with GPR40-specific small interfering RNA significantly reduced the decrease in K+ current induced by linoleic acid, whereas the cAMP-induced reduction of K+ current was not affected. We conclude that linoleic acid reduces the voltage-gated K+ current in rat β-cells through GPR40 and the cAMP-protein kinase A system, leading to an increase in [Ca2+]i and insulin secretion.

scholarly journals Regulation of Tyrosine Phosphatase STEP61 by Protein Kinase A during Motor Skill Learning in Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86988 ◽  
Author(s):  
Laure Chagniel ◽  
Yan Bergeron ◽  
Geneviève Bureau ◽  
Guy Massicotte ◽  
Michel Cyr
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Motor Skill ◽  
Tyrosine Phosphatase ◽  
Skill Learning ◽  
Motor Skill Learning ◽  
Kinase A

scholarly journals Antagonism of VEGF-A–induced increase in vascular permeability by an integrin α3β1-Shp-1-cAMP/PKA pathway

Blood ◽  
2012 ◽  
Vol 120 (24) ◽  
pp. 4892-4902 ◽  
Author(s):  
Soo Hyeon Kim ◽  
Young-Rak Cho ◽  
Hyeon-Ju Kim ◽  
Joa Sub Oh ◽  
Eun-Kyung Ahn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Vascular Permeability ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Vascular Endothelial ◽  
Protein Tyrosine ◽  
Vascular Endothelial Cadherin ◽  
Integrin Α3β1 ◽  
Kinase A

Abstract In cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A–induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells. All of these effects are completely ablated by selective knockdown of integrin α3β1 expression, expression of a dominant negative protein tyrosine phosphatase Shp-1 mutant, administration of the protein tyrosine phosphatase inhibitor orthovanadate, or the adenylate cyclase inhibitor SQ22536. This TIMP-2–mediated inhibition of vascular permeability involves an integrin α3β1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association, as evidenced by using siRNAs to integrin α3β1 and Shp-1, or treatment with Shp-1 inhibitor NSC87877 and protein kinase A inhibitor H89. Our results demonstrate the potential utility for TIMP-2 in cancer therapy through “normalization” of vascular permeability in addition to previously described antiangiogenic effects.

scholarly journals Correction: Regulation of Tyrosine Phosphatase STEP61 by Protein Kinase A during Motor Skill Learning in Mice

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150220 ◽  
Author(s):  
Laure Chagniel ◽  
Yan Bergeron ◽  
Geneviève Bureau ◽  
Guy Massicotte ◽  
Michel Cyr
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Motor Skill ◽  
Tyrosine Phosphatase ◽  
Skill Learning ◽  
Motor Skill Learning ◽  
Kinase A

Activation of mGluR5 modulates Ca2+currents in retinal amacrine cells from the chick

2004 ◽  
Vol 21 (6) ◽  
pp. 807-816 ◽  
Author(s):  
ROMINA SOSA ◽  
EVANNA GLEASON
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Glutamate Receptors ◽  
Amacrine Cells ◽  
Voltage Gated ◽  
Metabotropic Glutamate ◽  
Direct Activation ◽  
Voltage Dependent ◽  
Kinase A ◽  
Stimulation Of

In the inner plexiform layer, amacrine cells receive glutamatergic input from bipolar cells. Glutamate can depolarize amacrine cells by activation of ionotropic glutamate receptors or mediate potentially more diverse changesviaactivation of G protein-coupled metabotropic glutamate receptors (mGluR5). Here, we asked whether selective activation of metabotropic glutamate receptor 5 is linked to modulation of the voltage-gated Ca2+channels expressed by cultured GABAergic amacrine cells. To address this, we performed whole-cell voltage clamp experiments, primarily in the perforated-patch configuration. We found that agonists selective for mGluR5, including (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), enhanced the amplitude of the voltage-dependent Ca2+current. The voltage-dependent Ca2+current and CHPG-dependent current enhancement were blocked by nifedipine, indicating that L-type Ca2+channels, specifically, were being modulated. We have previously shown that activation of mGluR5 produces Ca2+elevations in cultured amacrine cells (Sosa et al., 2002). Loading the cells with 5 mM BAPTA inhibited the mGluR5-dependent enhancement, suggesting that the cytosolic Ca2+elevations are required for modulation of the current. Although activation of mGluR5 is typically linked to activation of protein kinase C, we found that direct activation of this kinase leads to inhibition of the Ca2+current, indicating that stimulation of this enzyme is not responsible for the mGluR5-dependent enhancement. Interestingly, direct stimulation of protein kinase A produced an enhancement of the Ca2+current similar to that observed with activation of mGluR5. Thus, activation of mGluR5 may modulate the L-type voltage-gated Ca2+current in these GABAergic amacrine cellsviaactivation of protein kinase A, possiblyviadirect activation of a Ca2+-dependent adenylate cyclase.

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