Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have evaluated the regulation of the nonmuscle alkali myosin light chain isoform, MLC3nm, in mouse C2 myoblasts, in vitro. We altered the normal MLC mRNA profile of these cells, using stable transfection to introduce an exogenous pool of human MLC3nm mRNA. We used an isoform-specific, species-specific mouse MLC3nm cDNA probe to examine the response of the endogenous gene to the exogenous expression. At high cell density, expression of the endogenous mouse MLC3nm mRNA in transfectants is reduced to 50-70% of that in vector-transfected controls. These results suggest that a feedback mechanism operates in vitro, to regulate the size of the total MLC3nm mRNA pool. The down regulation of the mRNA for endogenous isoform is not detected at low cell density, suggesting that the mechanism may be density dependent and related to myoblast differentiation.
Cell Mol Biol Res 1994
PMID:Regulation of nonmuscle myosin light chain 3 gene expression in response to exogenous MLC3nm mRNA. 780 26

The fact that smooth muscle exists in almost every hollow organ and is involved in a large number of disease states has led to a vast increase in smooth muscle research, covering areas from testing response to antagonists and agonists to measuring the molecular force generated by a single actin filament. Yet, the exact mechanisms regulating contractile response of smooth muscle remain unsolved. Calcium has been a central player in mediating smooth muscle contraction through binding with calmodulin, although there is evidence showing that under special circumstances smooth muscle can contract without change in intracellular Ca2+. In addition to the major regulatory pathway of Ca(2+)-calmodulin-myosin light chain kinase, there are other thin filament linked regulatory mechanisms in which Ca(2+)-calmodulin dependent phosphorylation of calponin and caldesmon may be involved. Ca2+ sensitivity of smooth muscle contraction may vary under different situations and this has recently been recognized as an important regulatory mechanism. Examples are protein kinase C (PKC) dependent phosphorylation of myosin light chain kinase which results in partial inhibition of contraction, and activation of myosin light chain phosphatase. There is new evidence showing that not only does Ca2+ regulate contraction by regulating the interaction of contractile proteins in smooth muscle, but also that shortening of smooth muscle itself reduces intracellular Ca2+ concentration, via a negative feedback.
Mol Cell Biochem 1994 Jun 15
PMID:Calcium and smooth muscle contraction. 781 50

In this article we review the various amino acids present in vertebrate nonmuscle and smooth muscle myosin that can undergo phosphorylation. The sites for phosphorylation in the 20 kD myosin light chain include serine-19 and threonine-18 which are substrates for myosin light chain kinase and serine-1 and/or -2 and threonine-9 which are substrates for protein kinase C. The sites in vertebrate smooth muscle and nonmuscle myosin heavy chains that can be phosphorylated by protein kinase C and casein kinase II are also summarized. Original data indicating that treatment of human T-lymphocytes (Jurkat cell line) with phorbol 12-myristate 13-acetate results in phosphorylation of both the 20 kD myosin light chain as well as the 200 kD myosin heavy chain is presented. We identified the amino acids phosphorylated in the human T-lymphocytes myosin light chains as serine-1 or serine-2 and in the myosin heavy chains as serine-1917 by 1-dimensional isoelectric focusing of tryptic phosphopeptides. Untreated T-lymphocytes contain phosphate in the serine-19 residue of the myosin light chain, and in a residue tentatively identified as serine-1944 in the myosin heavy chain.
Mol Cell Biochem 1993 Nov
PMID:Phosphorylation of vertebrate nonmuscle and smooth muscle myosin heavy chains and light chains. 793 53

Phosphorylation of the regulatory light chain of myosin by the Ca2+/calmodulin-dependent myosin light chain kinase plays an important role in smooth muscle contraction, nonmuscle cell shape changes, platelet contraction, secretion, and other cellular processes. Smooth muscle myosin light chain kinase is also phosphorylated, and recent results from experiments designed to satisfy the criteria of Krebs and Beavo for establishing the physiological significance of enzyme phosphorylation have provided insights into the cellular regulation and function of this phosphorylation in smooth muscle. The multifunctional Ca2+/calmodulin-dependent protein kinase II phosphorylates myosin light chain kinase at a regulatory site near the calmodulin-binding domain. This phosphorylation increases the concentration of Ca2+/calmodulin required for activation and hence increases the Ca2+ concentrations required for myosin light chain kinase activity in cells. However, the concentration of cytosolic Ca2+ required to effect myosin light chain kinase phosphorylation is greater than that required for myosin light chain phosphorylation. Phosphorylation of myosin light chain kinase is only one of a number of mechanisms used by the cell to down regulate the Ca2+ signal in smooth muscle. Since both smooth and nonmuscle cells express the same form of myosin light chain kinase, this phosphorylation may play a regulatory role in cellular processes that are dependent on myosin light chain phosphorylation.
Mol Cell Biochem 1993 Nov
PMID:Phosphorylation of myosin light chain kinase: a cellular mechanism for Ca2+ desensitization. 793 54

We have reported that myosin light chain phosphorylation is increased in contracting airway smooth muscle from hyperresponsive, ragweed pollen-sensitized dogs. This alteration is manifest physiologically in smooth muscle tissue from sensitized animals as it demonstrates faster shortening velocity and increased shortening capacity. One of the mechanisms underlying the defect is increased myosin light chain kinase activity; it is not known whether modulation of myosin phosphatase activity contributes to enhanced myosin light chain phosphorylation in sensitized canine smooth muscle. We describe a myosin phosphatase assay that we have used to compare the enzyme's activity in crude tracheal smooth muscle tissue homogenates from control and sensitized airway smooth muscle. Twenty kilodalton myosin light chain phosphorylation was initiated with Mg(2+)-ATP, and maximum levels were reached within 40 s; peak phosphorylation levels were stable for at least 3 min. The relative stoichiometry of 20 kD myosin light chain phosphorylation was estimated by chemiluminescent immunoblot assay. Smooth muscle phosphatase activity was estimated by the rate of decline in peak light chain phosphorylation, while myosin light chain kinase was inhibited indirectly with trifluoperazine, with EGTA, or directly by a synthetic peptide inhibitor. Okadaic acid, an inhibitor of phosphatase activity, curbed the decline in light chain phosphorylation seen after myosin light chain kinase inhibition, indicating that the light chain dephosphorylation observed was the result of smooth muscle phosphatase activity. Addition of okadaic acid to the samples led to a 30 to 40% increase in the peak myosin light chain phosphorylation attained for all samples. This indicates that similar populations of phosphatases were present in the homogenates of both control and sensitized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Dec
PMID:Myosin light chain phosphatase activity in ragweed pollen-sensitized canine tracheal smooth muscle. 794 96

We studied the extent of Ca2+ influx, myoplasmic free Ca2+ concentration changes, and phosphorylation of the regulatory 20-kDa myosin light chain (LC20) associated with the potentiation of stretch-induced myogenic tone in the rabbit facial vein. The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), was used to augment Ca(2+)-dependent stretch-induced myogenic tone. Veins stretched to an optimal resting tension in physiological salt solution (PSS) containing 0.4 mM of Ca2+ developed stretch-induced myogenic tone. Tissues incubated in Ca(2+)-free PSS, either with or without PMA (0.1 microM) did not develop myogenic tone. Readmission of Ca2+ (0.4 mM) caused a three-fold increase in the contraction in PMA-treated segments (710 +/- 60 mg, n = 29 v control: 188 +/- 10 mg, n = 24). This increased contraction was not associated with additional increases in either Ca2+ influx (73.5 +/- 6.9 pmol/mg of tissue/min, n = 29 v control: 61.1 +/- 5.7 pmol/mg of tissue/min, n = 24), myoplasmic free Ca2+ concentration or LC20, (0.44 +/- 0.02 mol PO4/mol LC20, n = 9 v control: 0.43 +/- 0.03 mol PO4/mol LC20, n = 7). Our results suggest that PKC activation amplifies stretch-induced myogenic tone in the rabbit facial vein through target proteins that are not associated with regulation of Ca2+ influx, myoplasmic free Ca2+ concentration, or LC20 phosphorylation. We conclude that the PKC-mediated potentiation of stretch-induced myogenic tone is due to an increased sensitivity of the contractile apparatus to Ca2+.
J Mol Cell Cardiol 1994 Mar
PMID:Phorbol ester-induced potentiation of myogenic tone is not associated with increases in Ca2+ influx, myoplasmic free Ca2+ concentration, or 20-kDa myosin light chain phosphorylation. 802 13

Muscle weakness in glucocorticoid myopathy results mainly from muscle atrophy, the reason for which is the accelerated catabolism of muscle proteins. As the content of lysosomes in skeletal muscle, particularly in fast-twitch glycolytic fibers, is relatively low the non-lysosomal pathway makes a particularly significant contribution and has special importance in the initial rate-limiting steps in the catabolism of contractile proteins and in the regulation of their turnover rate. The turnover rate of actin and the myosin heavy chain is decreased in all types of muscle fibers, and more rapid turnover of the myosin light chain is registered in the fast-twitch glycolytic and oxidative-glycolytic fibers. Exercise and simultaneous glucocorticoid treatment is an effective measure in retarding skeletal muscle atrophy and provides protection against muscle wasting.
J Steroid Biochem Mol Biol 1994 Jul
PMID:Turnover of skeletal muscle contractile proteins in glucocorticoid myopathy. 804 26

Based on previous immunological data, cross-reactivity of myosin heavy chain (MHC) with the ventricular (V) isoform was observed in primordia of avian skeletal muscles and in regenerating adult anterior latissimus dorsi (ALD) muscle. To determine whether this primordial (P) MHC is identical to adult V-MHC gene product, we have cloned and characterized the 3' portion of MHC cDNA that is expressed in ALD muscle at 3 d of regeneration. Comparison of nucleotide sequences between adult V-MHC and P-MHC cDNAs revealed more than 98% homology in the 3'-untranslated (UT) portions of these genes. The expression pattern of P-MHC was analyzed in adult regenerating muscles using total RNA from two fast muscles, posterior latissimus dorsi (PLD) and pectoralis major (PM), as well as from slow ALD and mixed fast/slow gastrocnemius muscles at 0, 1, 3, 4, 6, 9, and 14 d after cold injury. Identical results were obtained by RNase protection assays using either a probe specifying the coding region of adult V-MHC or a P-MHC probe encoding the carboxy end plus the 3'-UT region. The expected protected fragments were detected early from day 2 up to day 6 in ALD muscle. Similar rate of appearance, reaching the highest level at day 3, was observed in PLD, PM, and gastrocnemius muscles. However, the amount and the kinetics of disappearance differed among the various muscles analyzed. In contrast, during development, steady-state levels and kinetics of V-MHC mRNA expression were found to be alike in axial and appendicular muscles. These data strongly suggest the identity of P-MHC as the ventricular isoform and support the concept that expression of P-MHC mRNA is a common feature of developing as well as of all regenerating adult skeletal muscles. Interestingly, no expression of cardiac specific myosin light chain (MLC) 2A was observed after cold injury, suggesting independent regulatory pathways for the two kinds of myosin subunits.
Cell Mol Biol Res 1993
PMID:Differential expression of ventricular-like myosin heavy chain mRNA in developing and regenerating avian skeletal muscles. 817 88

Eleven Entamoeba histolytica protein-serine/threonine-kinase gene segments were identified using the polymerase chain reaction (PCR) and degenerate oligonucleotide primers to conserved amino acids in subdomains VI and VIII of the catalytic domain of protein-serine/threonine kinases. These ameba gene segments were homologous to myosin light chain kinases, protein kinase C, phosphorylase b kinase, and kinases that regulate glucose repression in yeast and cell growth in mammalian cells. One of these PCR products, which was homologous to the Dictyostelium discoideum protein kinase 2, was used to identify a full-length protein-serine/threonine-kinase gene (Eh rac1) from an E. histolytica genomic library. The open reading frame of Eh rac1 was 409 amino acids long (encoding a 47-kDa protein) and included an amino terminal segment containing 87 mostly charged and polar amino acids and a 322-amino acid carboxyl terminal segment containing the catalytic domain. The catalytic domain of Eh rac1 was homologous to the rac family of protein-serine/threonine-kinases, which are related to cAMP-dependent protein kinases and protein kinase Cs. Southern blots of ameba DNA showed that the Eh rac1 gene was present as a single copy in all strains tested, however pathogenic amebae expressed four times more Eh rac1 mRNAs than did nonpathogenic amebae. These studies suggest that E. histolytica, a primitive unicellular eukaryote, has a complex protein kinase family.
Mol Biochem Parasitol 1993 Aug
PMID:Molecular cloning of a rac family protein kinase and identification of a serine/threonine protein kinase gene family of Entamoeba histolytica. 823 9

During development of the human heart, the atrial isoform of alkali myosin light chain (MLC1A) is expressed in the ventricle. With maturation of the heart, MLC1A expression is completely replaced by that of the adult ventricular myosin light chain, MLC1V. We have evaluated the re-expression of MLC1A as a marker of different disease states of the human ventricle. RNA was isolated from the ventricles of patients with idiopathic dilated cardiomyopathy (CM) and severe congenital cardiac defects (CCD). Northern blot analysis was used to measure the mRNA levels of MLC1A and MLC1V in these samples. As a control, the level of regulatory MLC2V mRNA was also measured. We find that the level of MLC2V mRNA per microgram total ventricular RNA is very similar in CM, CCD and normal human samples. In contrast, we find that MLC1V mRNA levels tend to be reduced in both CM and CCD samples. In the case of the CCD samples, this apparent drop in MLC1V is compensated by expression of the developmental MLC1A isoform. However, in CM patients in end-stage failure, expression of MLC1A is barely detectable. The expression of MLC1A in CCD samples may reflect an adaptive mechanism in response to cardiac overload. The failure to detect substantial MLC1A expression in the CM samples may reflect the failure of such an adaptive mechanism.
J Mol Cell Cardiol 1993 May
PMID:Myosin light chain gene expression associated with disease states of the human heart. 837 17


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