Myosin light chain kinase: functional domains and structural motifs

Lin, Pei Ju; Krueger, Joanna K.; Trewhella, Jill; Zhi, Gang

doi:10.1111/j.1365-201x.1998.tb10699.x

Cited by 73 publications

(69 citation statements)

References 68 publications

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“…Therefore, our results also indicate that maintenance of a normal concentration of Ca 2＋ in extracellular fluid may be necessary for transmitter release upon nerve activation by EFS and for the triggering of an excitation-contraction coupling mechanism in esophageal smooth muscle [26]. MLCK, another intracellular mediator that is activated in an intracellular Ca 2＋ /calmodulin-dependent manner, plays an important role in force development in smooth muscle [27]. According to our results, ML-9 significantly inhibited EFSinduced off-contraction in a concentration-dependent manner.…”

Section: Discussionsupporting

confidence: 52%

MLCK and PKC Involvements via Gi and Rho A Protein in Contraction by the Electrical Field Stimulation in Feline Esophageal Smooth Muscle

Park

Shim

Kim

et al. 2010

Korean J Physiol Pharmacol

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W e have shown that myosin light chain kinase (MLCK) was required for the off-contraction in response to the electrical field stimulation (EFS) of feline esophageal smooth muscle. In this study, we investigated whether protein kinase C (PKC) may require the on-contraction in response to EFS using feline esophageal smooth muscle. The contractions were recorded using an isometric force transducer. On-contraction occurred in the presence of N G -nitro-L-arginine methyl ester (L-NAME), suggesting that nitric oxide acts as an inhibitory mediator in smooth muscle. The excitatory composition of both contractions was cholinergic dependent which was blocked by tetrodotoxin or atropine. The on-contraction was abolished in Ca 2＋ -free buffer but reappeared in normal Ca 2＋ -containing buffer indicating that the contraction was Ca 2＋ dependent. 4-aminopyridine (4-AP), voltage-dependent K＋ channel blocker, significantly enhanced on-contraction. Aluminum fluoride (a G-protein activator) increased on-contraction. Pertussis toxin (a Gi inactivator) and C3 exoenzyme (a rhoA inactivator) significantly decreased on-contraction suggesting that Gi or rhoA protein may be related with Ca 2＋ and K ＋ channel. ML-9, a MLCK inhibitor, significantly inhibited on-contraction, and chelerythrine (PKC inhibitor) affected on the contraction. These results suggest that endogenous cholinergic contractions activated directly by low-frequency EFS may be mediated by Ca 2＋ , and G proteins, such as Gi and rhoA, which resulted in the activation of MLCK, and PKC to produce the contraction in feline distal esophageal smooth muscle.

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Section: Discussionsupporting

confidence: 52%

MLCK and PKC Involvements via Gi and Rho A Protein in Contraction by the Electrical Field Stimulation in Feline Esophageal Smooth Muscle

Park

Shim

Kim

et al. 2010

Korean J Physiol Pharmacol

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“…Consistent with a kinase-independent mechanism, L-MLCK-specific N-terminal sequences (Fig. 11A), which lack the myosin-binding and kinase domains (Stull et al, 1998) but bundle actin filaments (Smith et al, 2002;Yang et al, 2006), slowed the rate of cell spreading by 30-53% (Fig. 11B).…”

Section: Mediation Via Mlckmentioning

confidence: 53%

“…Myosin II and actin filaments have long been known to assemble at the membrane surface (DeBiasio et al, 1988;McKenna et al, 1989;Rhee et al, 1994) and to interact with both L-MLCK and S-MLCK (Blue et al, 2002;Dulyaninova et al, 2004;Poperechnaya et al, 2000;Stull et al, 1998). The additional F-actin-binding and -bundling sequences in the unique L-MLCK N-terminus apparently increase the affinity of L-MLCK, relative to S-MLCK, for actin filaments (Smith et al, 2002;Yang et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Murine L-MLCK contains the entire S-MLCK coding sequence. In addition, L-MLCK contains an extra N-terminal sequence of 954 amino acids with multiple actin-binding sites within its immunoglobulin (Ig) domains and two DXR repeats (repeats of a motif made up of the sequence DXRXXL) (Kudryashov et al, 2004;Poperechnaya et al, 2000;Smith et al, 2002;Stull et al, 1998;Yang et al, 2006). The shared S-MLCK C-terminus contains another three DXR repeats, the kinase domain and a myosin II-binding site (Fig.…”

Section: Mediation Via Mlckmentioning

confidence: 99%

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Supervillin slows cell spreading by facilitating myosin II activation at the cell periphery

Takizawa

Ikebe

et al. 2007

Journal of Cell Science

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“…Although MLC kinase can be regulated by [Ca 2ϩ ] i (78,79), the MLC phosphatases are regulated by Rho kinase (80). Hence, activation of Rho in HMEC-1 could result in the inactivation of MLC phosphatases, favoring the phosphorylated state of MLC (30,81,82), making the pathway calcium-independent.…”

Section: Figmentioning

confidence: 99%

Functional Selectivity of G Protein Signaling by Agonist Peptides and Thrombin for the Protease-activated Receptor-1

McLaughlin

Shen

Holinstat

et al. 2005

Journal of Biological Chemistry

179

182

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Thrombin activates protease-activated receptor-1 (PAR-1) by cleavage of the amino terminus to unmask a tethered ligand. Although peptide analogs can activate PAR-1, we show that the functional responses mediated via PAR-1 differ between the agonists. Thrombin caused endothelial monolayer permeability and mobilized intracellular calcium with EC 50 values of 0.1 and 1.7 nM, respectively. The opposite order of activation was observed for agonist peptide (SFLLRN-CONH 2 or TFLL-RNKPDK) activation. The addition of inactivated thrombin did not affect agonist peptide signaling, suggesting that the differences in activation mechanisms are intramolecular in origin. Although activation of PAR-1 or PAR-2 by agonist peptides induced calcium mobilization, only PAR-1 activation affected barrier function. Induced barrier permeability is likely to be G␣ 12/13 -mediated as chelation of G␣ q -mediated intracellular calcium with BAPTA-AM, pertussis toxin inhibition of G␣ i/o , or GM6001 inhibition of matrix metalloproteinase had no effect, whereas Y-27632 inhibition of the G␣ 12/13 -mediated Rho kinase abrogated the response. Similarly, calcium mobilization is G␣ q -mediated and independent of G␣ i/o and G␣ 12/13 because pertussis toxin and Y-27632 had no effect, whereas U-73122 inhibition of phospholipase C-␤ blocked the response. It is therefore likely that changes in permeability reflect G␣ 12/13 activation, and changes in calcium reflect G␣ q activation, implying that the pharmacological differences between agonists are likely caused by the ability of the receptor to activate G␣ 12/13 or G␣ q . This functional selectivity was characterized quantitatively by a mathematical model describing each step leading to Rho activation and/or calcium mobilization. This model provides an estimate that peptide activation alters receptor/G protein binding to favor G␣ q activation over G␣ 12/13 by ϳ800-fold.

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Myosin light chain kinase: functional domains and structural motifs

Cited by 73 publications

References 68 publications

MLCK and PKC Involvements via Gi and Rho A Protein in Contraction by the Electrical Field Stimulation in Feline Esophageal Smooth Muscle

MLCK and PKC Involvements via Gi and Rho A Protein in Contraction by the Electrical Field Stimulation in Feline Esophageal Smooth Muscle

Supervillin slows cell spreading by facilitating myosin II activation at the cell periphery

Functional Selectivity of G Protein Signaling by Agonist Peptides and Thrombin for the Protease-activated Receptor-1

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