Ca2+-independent Smooth Muscle Contraction

Smooth muscle contraction follows an increase in cytosolic Ca2+ concentration, activation of myosin light chain kinase, and phosphorylation of the 20-kDa light chain of myosin at Ser19. Several agonists acting via G protein-coupled receptors elicit a contraction without a change in [Ca2+] i via inhibition of myosin light chain phosphatase and increased myosin phosphorylation. We showed that microcystin (phosphatase inhibitor)-induced contraction of skinned smooth muscle occurred in the absence of Ca2+ and correlated with phosphorylation of myosin light chain at Ser19 and Thr18 by a kinase distinct from myosin light chain kinase. In this study, we identify this kinase as integrin-linked kinase. Chicken gizzard integrin-linked kinase cDNA was cloned, sequenced, expressed in E. coli, and shown to phosphorylate myosin light chain in the absence of Ca2+ at Ser19 and Thr18. Subcellular fractionation revealed two distinct populations of integrin-linked kinase, including a Triton X-100-insoluble component that phosphorylates myosin in a Ca2+-independent manner. These results suggest a novel function for integrin-linked kinase in the regulation of smooth muscle contraction via Ca2+-independent phosphorylation of myosin, raise the possibility that integrin-linked kinase may also play a role in regulation of nonmuscle motility, and confirm that integrin-linked kinase is indeed a functional protein-serine/threonine kinase.

• Publication year

  2001

• Venue

  Journal of Biological Chemistry

• Publication date

  2001-05-11

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M011634200PMID 11278951
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Stimulus-specific patterns of myosin light chain phosphorylation in smooth muscle of rabbit thoracic artery

  2004cited by this paper
• Agonists Trigger G Protein-mediated Activation of the CPI-17 Inhibitor Phosphoprotein of Myosin Light Chain Phosphatase to Enhance Vascular Smooth Muscle Contractility*

  2000cited by this paper
• Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction.

  2000cited by this paper
• Inhibition of Rho‐associated kinase blocks agonist‐induced Ca2+ sensitization of myosin phosphorylation and force in guinea‐pig ileum

  2000cited by this paper
• Signal transduction by G‐proteins, Rho‐kinase and protein phosphatase to smooth muscle and non‐muscle myosin II

  2000cited by this paper
• Calmodulin: a prototypical calcium sensor.

  2000cited by this paper
• Integrin-linked kinase (ILK): a regulator of integrin and growth-factor signalling.

  1999cited by this paper
• Ca2+‐independent myosin II phosphorylation and contraction in chicken embryo fibroblasts

  1999cited by this paper
• PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2.

  1999cited by this paper
• Ca2+‐independent phosphorylation of myosin in rat caudal artery and chicken gizzard myofilaments

  1999cited by this paper
• Integrin-linked kinase regulates phosphorylation of serine 473 of protein kinase B by an indirect mechanism

  1999cited by this paper
• Rho-associated Kinase of Chicken Gizzard Smooth Muscle*

  1999cited by this paper
• Myosin light chain phosphatase: subunit composition, interactions and regulation

  1998cited by this paper
• p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13.

  1998cited by this paper
• Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase.

  1998cited by this paper
• Possible involvement of the novel CPI‐17 protein in protein kinase C signal transduction of rabbit arterial smooth muscle

  1998cited by this paper
• p115 RhoGEF, a GTPase activating protein for Gα12 and Gα13

  1998cited by this paper
• Reduced outward K+ conductances generate depolarizing after–potentials in rat supraoptic nucleus neurones

  1997cited by this paper
• Possible role of atypical protein kinase C activated by arachidonic acid in Ca2+ sensitization of rabbit smooth muscle.

  1997cited by this paper
• Myosin light chain kinases

  1997cited by this paper
• Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinase

  1996cited by this paper
• Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)

  1996cited by this paper
• Phosphorylation of the Large Subunit of Myosin Phosphatase and Inhibition of Phosphatase Activity (*)

  1996cited by this paper
• Interactions and properties of smooth muscle myosin phosphatase.

  1996cited by this paper
• Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).

  1995cited by this paper
• Signal transduction and regulation in smooth muscle

  1994cited by this paper
• The biochemical basis of the regulation of smooth-muscle contraction.

  1994cited by this paper
• A molecular mechanism for autoinhibition of myosin light chain kinases.

  1993cited by this paper
• Rapid amplification of complementary DNA ends for generation of full-length complementary DNAs: thermal RACE.

  1993cited by this paper
• Structural basis of the intrasteric regulation of myosin light chain kinases.

  1992cited by this paper
• Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium.

  1992cited by this paper
• Calcium ion homeostasis in smooth muscle.

  1992cited by this paper
• A novel protein kinase homolog essential for protein sorting to the yeast lysosome-like vacuole.

  1991cited by this paper
• mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.

  1991cited by this paper
• Phosphorylation of smooth muscle myosin by type II Ca2+/calmodulin-dependent protein kinase

  1990cited by this paper
• Mode of inhibition of smooth muscle myosin light chain kinase by synthetic peptide analogs of the regulatory site.

  1990cited by this paper
• Potent peptide inhibitors of smooth muscle myosin light chain kinase: mapping of the pseudosubstrate and calmodulin binding domains.

  1990cited by this paper
• Smooth muscle calponin. Inhibition of actomyosin MgATPase and regulation by phosphorylation.

  1990cited by this paper
• Location of the inhibitory region of smooth muscle myosin light chain kinase.

  1989cited by this paper
• The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.

  1988cited by this paper
• Sites phosphorylated in myosin light chain in contracting smooth muscle.

  1988cited by this paper
• Regional changes in calcium underlying contraction of single smooth muscle cells.

  1987cited by this paper
• Identification, phosphorylation, and dephosphorylation of a second site for myosin light chain kinase on the 20,000-dalton light chain of smooth muscle myosin.

  1986cited by this paper
• Calcium transients and resting levels in isolated smooth muscle cells as monitored with quin 2.

  1986cited by this paper
• Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase.

  1985cited by this paper
• Isolation of the native form of chicken gizzard myosin light-chain kinase.

  1984cited by this paper
• Selective purification of the 20,000-Da light chains of smooth muscle myosin.

  1983cited by this paper
• Squalene in Petroleum Asphaltenes

  1981cited by this paper
• Determination of nucleotide sequences in DNA

  1981cited by this paper
• Phosphorylation of smooth muscle myosin: evidence for cooperativity between the myosin heads.

  1981cited by this paper
• Determination of nucleotide sequences in DNA.

  1981cited by this paper

• ARHGAP36 imposes a bifurcate activation of adherens junction and actomyosin to promote entosis.

  2026cites this paper
• Regulation of Vascular Tone of Preglomerular Renal Vasculature by Caldesmon.

  2026cites this paper
• MLC2: Physiological Functions and Potential Roles in Tumorigenesis

  2025cites this paper
• Aging related decreases in NM myosin expression and contractility in a resistance vessel

  2024cites this paper
• p90RSK2, a new MLCK, rescues contractility in myosin light chain kinase null smooth muscle

  2023cites this paper
• Potentiation of active force by cyclic strain in sheep carotid arterial smooth muscle.

  2023cites this paper
• Vascular Mechanotransduction.

  2023cites this paper
• p90RSK2, a new MLCK mediates contractility in myosin light chain kinase null smooth muscle

  2023cites this paper
• Myosin light chain phosphorylation exhibits a gradient across the wall of cerebellar arteries under sustained ex vivo vascular tone

  2023cites this paper
• Multi-Omics of Familial Thoracic Aortic Aneurysm and Dissection: Calcium Transport Impairment Predisposes Aortas to Dissection

  2023cites this paper
• Mitotic protein kinase-driven crosstalk of machineries for mitosis and metastasis

  2022cites this paper
• Integrin-linked kinase (ILK): the known vs. the unknown and perspectives

  2022cites this paper
• Tas2R activation relaxes airway smooth muscle by release of Gαt targeting on AChR signaling

  2022cites this paper
• Impact of impaired cerebral blood flow autoregulation on cognitive impairment

  2022cites this paper
• Postnatal development alters functional compartmentalization of myosin light chain kinase in ovine carotid arteries.

  2021cites this paper
• ZnO and TiO2 Nanocolloids: State of Mechanisms that Regulating the Motility of the Gastrointestinal Tract and the Hepatobiliary System

  2021cites this paper
• Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

  2021cites this paper
• Role of smooth muscle cells in Cardiovascular Disease

  2020cites this paper
• Regulation of Myosin Light-Chain Phosphatase Activity to Generate Airway Smooth Muscle Hypercontractility

  2020cites this paper
• Inhibition of neurogenic and thromboxane A2‐induced human prostate smooth muscle contraction by the integrin α2β1 inhibitor BTT‐3033 and the integrin‐linked kinase inhibitor Cpd22

  2020cites this paper
• Rho-associated kinase and zipper-interacting protein kinase, but not myosin light chain kinase, are involved in the regulation of myosin phosphorylation in serum-stimulated human arterial smooth muscle cells

  2019cites this paper
• Role of integrin-linked kinase in the hypoxia-induced phenotypic transition of pulmonary artery smooth muscle cells: Implications for hypoxic pulmonary hypertension.

  2019cites this paper
• Insulin attenuates apoptosis in neuronal cells by an integrin-linked kinase-dependent mechanism

  2019cites this paper
• Muscarinic m2 receptor‐mediated actin polymerization via PI3 kinase γ and integrin‐linked kinase in gastric smooth muscle

  2018cites this paper
• Vascular smooth muscle contraction in hypertension

  2018cites this paper
• Protective Effect of a Rho-kinase Inhibitor on Bladder Dysfunction in a Rat Model of Chronic Bladder Ischemia.

  2018cites this paper
• Sibutramine facilitates apoptosis and contraction of aortic smooth muscle cells through elevating production of reactive oxygen species

  2018cites this paper
• Gene expression profiles and signaling mechanisms in α2B-adrenoceptor-evoked proliferation of vascular smooth muscle cells

  2017cites this paper
• 13 Role of Protein Kinase Network in Excitation-Contraction Coupling in Smooth Muscle Cell

  2017cites this paper
• ILK (integrin-linked kinase)

  2017cites this paper
• Titanium Dioxide Modulation of the Contractibility of Visceral Smooth Muscles In Vivo

  2017cites this paper
• Highly sensitive myosin phosphorylation analysis in the renal afferent arteriole

  2016cites this paper
• to airway hyperresponsiveness in asthma? the contribution of airway smooth muscle contraction Invited Review: Do inflammatory mediators influence

  2015cites this paper
• Endothelin-1, but not angiotensin II, induces afferent arteriolar myosin diphosphorylation as a potential contributor to prolonged vasoconstriction.

  2015cites this paper
• Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma

  2015cites this paper
• Regulation of Smooth Muscle Dystrophin and Synaptopodin 2 Expression by Actin Polymerization and Vascular Injury

  2015cites this paper
• Pelvic arterial occlusive disease affects the RhoA/Rho-kinase pathway in bladder smooth muscle.

  2015cites this paper
• Nicotine and Integrin Linked Kinase Interplay Modulates Synaptic Plasticity Mechanisms Required for Memory

  2015cites this paper
• Functional Characterization of the Kinase and Pseudokinase Domains in the Janus Tyrosine Kinase (JAK) 2

  2014cites this paper
• Vascular Function in Health and Disease

  2014cites this paper
• The involvement of myosin regulatory light chain diphosphorylation in sustained vasoconstriction under pathophysiological conditions

  2014cites this paper
• The inhibitory effect of vitexin on the agonist-induced regulation of vascular contractility.

  2014cites this paper
• Novel Contributions of the Smoothelin‐like 1 Protein in Vascular Smooth Muscle Contraction and its Potential Involvement in Myogenic Tone

  2014cites this paper
• Differential phosphorylation of LZ+/LZ- MYPT1 isoforms regulates MLC phosphatase activity.

  2014cites this paper
• Inhibition of Gαi activity by Gβγ is mediated by PI 3-kinase-γ- and cSrc-dependent tyrosine phosphorylation of Gαi and recruitment of RGS12.

  2014cites this paper
• Rho Kinase Acts as a Downstream Molecule to Participate in Protein Kinase C&egr; Regulation of Vascular Reactivity After Hemorrhagic Shock in Rats

  2014cites this paper
• Myosin Light Chain Kinase (MLCK) Regulates Cell Migration in a Myosin Regulatory Light Chain Phosphorylation-independent Mechanism*

  2014cites this paper
• Effects of integrin‐linked kinase on human corpus cavernosum smooth muscle cell cytoskeletal organisation

  2013cites this paper
• The characteristics of genistin-induced inhibitory effects on intestinal motility

  2013cites this paper
• Membrane depolarization-induced RhoA/Rho-associated kinase activation and sustained contraction of rat caudal arterial smooth muscle involves genistein-sensitive tyrosine phosphorylation

  2013cites this paper
• The Inhibitory Effect of Eupatilin on the Agonist-Induced Regulation of Vascular Contractility

  2013cites this paper
• Prostate-apoptosis response-4 phosphorylation in vascular smooth muscle.

  2013cites this paper
• Ilk conditional deletion in adult animals increases cyclic GMP-dependent vasorelaxation.

  2013cites this paper
• Enhanced Depolarization-Induced Pulmonary Vasoconstriction Following Chronic Hypoxia Requires EGFR-Dependent Activation of NAD(P)H Oxidase 2

  2013cites this paper
• p38 mitogen-activated protein kinase mediates hyperosmolarity-induced vasoconstriction through myosin light chain phosphorylation and actin polymerization in rat aorta.

  2013cites this paper
• PDMS Elastic Micropost Arrays for Studying Vascular Smooth Muscle Cells.

  2013cites this paper
• The p90 Ribosomal S6 Kinase (RSK) Is a Mediator of Smooth Muscle Contractility

  2013cites this paper
• depending on adhesion of gastric carcinoma cells Epigenetic regulation of integrin-linked kinase expression

  2013cites this paper
• Signaling through Myosin Light Chain Kinase in Smooth Muscles*

  2013cites this paper
• GMP-DEPENDENT VASORELAXATION

  2013cites this paper
• Myosin Regulatory Light Chain Diphosphorylation Slows Relaxation of Arterial Smooth Muscle*

  2012cites this paper
• Decreased myosin phosphatase target subunit 1(MYPT1) phosphorylation via attenuated rho kinase and zipper‐interacting kinase activities in edematous intestinal smooth muscle

  2012cites this paper
• Identification and Characterization of a Novel Integrin-Linked

  2012cites this paper
• Biphasic Regulation of Myosin Light Chain Phosphorylation by p21-activated Kinase Modulates Intestinal Smooth Muscle Contractility*

  2012cites this paper
• Controversial Effect of Ethanol Irrespective of Kinases Inhibition on the Agonist-Dependant Vasoconstriction

  2012cites this paper
• Matrix compliance regulates Rac1b localization, NADPH oxidase assembly, and epithelial–mesenchymal transition

  2012cites this paper
• The regulation of myosin phosphatase in pregnant human myometrium.

  2012cites this paper
• Hypoxic pulmonary vasoconstriction.

  2012cites this paper
• New insights into the regulation of myosin light chain phosphorylation in retinal pigment epithelial cells.

  2012cites this paper
• The Inhibitory Effect of Quercetin on the Agonist-Induced Regulation of Vascular Contractility

  2011influential citation
• Integrin-linked kinase is an essential mediator of ERG-induced epithelial-to-mesenchymal transition in prostate cancer models

  2011cites this paper
• Chemical Genetics of Zipper-interacting Protein Kinase Reveal Myosin Light Chain as a Bona Fide Substrate in Permeabilized Arterial Smooth Muscle*

  2011cites this paper
• Rho-associated kinase plays a role in rabbit urethral smooth muscle contraction, but not via enhanced myosin light chain phosphorylation.

  2011cites this paper
• Biochemical, Proteomic, Structural, and Thermodynamic Characterizations of Integrin-linked Kinase (ILK)

  2011cites this paper
• Biochemistry of smooth muscle myosin light chain kinase.

  2011cites this paper
• Identification and characterization of a novel integrin-linked kinase inhibitor.

  2011cites this paper
• Enhanced contractility and myosin phosphorylation induced by Ca(2+)-independent MLCK activity in hypertensive rats.

  2011cites this paper
• Functional role of muscarinic receptor subtypes in calcium sensitization and their contribution to rho-kinase and protein kinase C pathways in contraction of human detrusor smooth muscle.

  2011cites this paper
• Integrin-linked kinase: a Scaffold protein unique among its ilk

  2011cites this paper
• MAPKs represent novel therapeutic targets for gastrointestinal motility disorders.

  2011cites this paper
• Integrin-linked kinase: Not so ‘pseudo’ after all

  2011influential citation
• mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen*

  2011cites this paper
• Phosphorylation and interaction of Myopodin by Integrin-Link Kinase Lead to Suppression of Cell Growth and Motility in Prostate Cancer Cells

  2011cites this paper
• Vascular smooth muscle myosin light chain diphosphorylation: Mechanism, function, and pathological implications

  2011cites this paper
• Aortic Aneurysm Generation in Mice With Targeted Deletion of Integrin-Linked Kinase in Vascular Smooth Muscle Cells

  2011cites this paper
• The Inhibitory Effect of Shikonin on the Agonist-Induced Regulation of Vascular Contractility

  2011cites this paper
• Expression of the Integrin-Linked Kinase in a Rat Kidney Model of Chronic Allograft Nephropathy

  2011cites this paper
• ILK mediates the effects of strain on intestinal epithelial wound closure.

  2011cites this paper
• Excitation–Contraction Coupling and Regulation of Pulmonary Vascular Contractility

  2011cites this paper
• Integrin-linked kinase 1: role in hormonal cancer progression.

  2011cites this paper
• HMC05 attenuates vascular contraction through inhibition of RhoA/Rho-kinase signaling pathway.

  2011cites this paper
• Myeloid lineage cells inhibit neurite outgrowth through a myosin II-dependent mechanism.

  2011cites this paper
• Association of aorta intima permeability with myosin light chain kinase expression in hypercholesterolemic rabbits

  2010cites this paper
• Evidence that actomyosin cross bridges contribute to "passive" tension in detrusor smooth muscle.

  2010cites this paper
• Kinase-related protein/telokin inhibits Ca2+-independent contraction in Triton-skinned guinea pig taenia coli.

  2010cites this paper
• Protective Effect of Resveratrol on Agonist-Dependent Regulation of Vascular Contractility via Inhibition of Rho-Kinase Activity

  2010cites this paper
• AMP-activated protein kinase induces actin cytoskeleton reorganization in epithelial cells.

  2010cites this paper
• Sphingosine-1-Phosphate–Dependent Activation of p38 MAPK Maintains Elevated Peripheral Resistance in Heart Failure Through Increased Myogenic Vasoconstriction

  2010cites this paper
• Kindlin‐2 is expressed in malignant mesothelioma and is required for tumor cell adhesion and migration

  2010cites this paper
• Modulation of Microvascular Smooth Muscle Adhesion and Mechanotransduction by Integrin‐Linked Kinase

  2010cites this paper