α5β1 Integrin Engagement Increases Large Conductance, Ca2+-activated K+ Channel Current and Ca2+ Sensitivity through c-src-mediated Channel Phosphorylation

Yang, Yan; Wu, Xin; Gui, Peichun; Wu, Jianbo; Sheng, Jian‐Zhong; Ling, Shizhang; Braun, Andrew P.; Davis, George E.; Davis, Michael J.

doi:10.1074/jbc.m109.033506

Cited by 43 publications

(50 citation statements)

References 60 publications

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“…We wondered whether this could be due to an effect on calcium flux through this receptor, as it was previously shown that ␣ 5 ␤ 1 engagement in human embryonic kidney-293 cells with fibronectin or an antibody increased cytosolic calcium concentration (47). Furthermore, calcium mobilization is important for cytoskeleton mobility and phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of TNF induction by heat-killed Staphylococcus aureus differ upon the origin of mononuclear phagocytes

Kapétanovic

Parlato

Fitting

et al. 2011

American Journal of Physiology-Cell Physiology

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Section: Discussionmentioning

confidence: 99%

Mechanisms of TNF induction by heat-killed Staphylococcus aureus differ upon the origin of mononuclear phagocytes

Kapétanovic

Parlato

Fitting

et al. 2011

American Journal of Physiology-Cell Physiology

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“…Integrin receptors and ion channels communicate by diffusible signals (16)(17)(18)(19)(20) as well as by forming macromolecular complexes (21)(22)(23)(24)(25). In particular, the b 1 integrin-mediated adhesion to fibronectin activates hERG1 currents (I hERG1 ) in different cell types (17,26).…”

Section: Introductionmentioning

confidence: 99%

The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression

et al. 2017

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Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K + flux through the human ether-à-gogo-related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the b 1 integrin subunit at the plasma membrane of human cancer cells. This interaction was not detected in cardiomyocytes because of the presence of the hERG1 auxiliary subunit KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1), which blocked the b 1 integrin-hERG1 interaction. Although open hERG1 channels did not interact as strongly with b 1 integrins as did closed channels, current flow through hERG1 channels was necessary to activate the integrin-dependent phosphorylation of Tyr 397 in focal adhesion kinase (FAK) in both normal and cancer cells. In immunodeficient mice, proliferation was inhibited in breast cancer cells expressing forms of hERG1 with impaired K + flow, whereas metastasis of breast cancer cells was reduced when the hERG1/b 1 integrin interaction was disrupted. We conclude that the interaction of b 1 integrins with hERG1 channels in cancer cells stimulated distinct signaling pathways that depended on the conformational state of hERG1 and affected different aspects of tumor progression.

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“…Second messenger involvement has been illustrated by an observed increase of 20-HETE production leading to inhibited BK Ca and vascular constriction upon an increase in intraluminal pressure (12). Additionally, a series of studies has focused on involvement of integrins as mechanotransductive structures important to the myogenic response (32,50,55). In these studies it has Previous studies have demonstrated that vessel strain is not a governing stimulus that can explain the myogenic response known to exist experimentally (4,21).…”

Section: Discussionmentioning

confidence: 99%

Mechanical control of cation channels in the myogenic response

Carlson

Beard

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Microcirculatory vessel response to changes in pressure, known as the myogenic response, is a key component of a tissue's ability to regulate blood flow. Experimental studies have not clearly elucidated the mechanical signal in the vessel wall governing steady-state reduction in vessel diameter upon an increase in intraluminal pressure. In this study, a multiscale computational model is constructed from established models of vessel wall mechanics, vascular smooth muscle (VSM) force generation, and VSM Ca 2ϩ handling and electrophysiology to compare the plausibility of vessel wall stress or strain as an effective mechanical signal controlling steady-state vascular contraction in the myogenic response. It is shown that, at the scale of a resistance vessel, wall stress, and not stretch (strain), is the likely physiological signal controlling the steady-state myogenic response. (28), and large-conductance, Ca 2ϩ -activated K ϩ (BK Ca ) channel, which has a large influence on the level of membrane polarization (17). Many of these studies identifying channels with mechanotransductive qualities have investigated the channels in isolation by patch clamping and exposure to exogenous substances or mechanical conditions representative of those thought to be present in the intact cellular environment. Foundational work on mechanotransductive channels focused on how the strain or tension directly affects channel-gating probabilities (39 -41). It is clear that many of these channels respond to mechanical stimulation; however, it cannot be determined from these studies whether vessel wall stress or strain is the controlling mechanical stimulus and how these stimuli may control channel function in the myogenic response. Therefore, to understand how these channels are controlled and play a role in the acute regulatory response to pressure through the complex interactions in an intact single vessel, an integrated theoretical model taking into consideration VSM electrophysiology, VSM force generation, and vessel wall mechanics must be employed. Such a theoretical platform is a valuable hypothesis-testing method aimed at assessing which underlying channel function or set of functions is sufficient to describe the observed whole-vessel response and will be important in determining future experimental design.Several detailed models of VSM electrophysiology have been previously developed and used in integrated models of acute regulation of arteriolar vessels. Yang et al. (53,54) -induced Ca 2ϩ release and cytosolic buffering. Simulation protocols utilizing a depolarizing voltage pulse and applied strain were used to interrogate the model function with respect to qualitative and quantitative features from experimental studies of VSM cells. Koenigsberger et al. (24,25) investigated the myogenic response and oscillatory behavior of microvessels known as vasomotion with a similar model but focused on the influence of stretch-activated channels that were formulated to be activated by stress in the vessel. VSM force generation based on cy...

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α5β1 Integrin Engagement Increases Large Conductance, Ca2+-activated K+ Channel Current and Ca2+ Sensitivity through c-src-mediated Channel Phosphorylation

Cited by 43 publications

References 60 publications

Mechanisms of TNF induction by heat-killed Staphylococcus aureus differ upon the origin of mononuclear phagocytes

Mechanisms of TNF induction by heat-killed Staphylococcus aureus differ upon the origin of mononuclear phagocytes

The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression

Mechanical control of cation channels in the myogenic response

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