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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular calcium levels play an important role in myofibril disintegration and regeneration of muscle fibers. Earlier studies have shown that the calcium activated protease, calpain, is involved in the removal of Z-discs from myofibrils of striated muscle and the tripeptide-aldehyde, leupeptin, which is an inhibitor of calpain, inhibits this activity. In the present communication, we demonstrate that leupeptin and another calpain inhibitor, E64d, inhibit the fusion of mouse skeletal muscle C2C12 myoblasts to form multinucleated myotubes in tissue culture.
Cell Mol Biol 1992 Aug
PMID:The effect of protease inhibitors, leupeptin and E64d, on differentiation of C2C12 myoblasts in tissue culture. 146 8

Intracellular calcium levels play an important role in myofibril disintegration and regeneration of muscle fibers. Earlier studies have shown that the calcium activated protease, calpain, is involved in the removal of Z-discs from myofibrils of striated muscle and the tripeptide-aldehyde, leupeptin, which is an inhibitor of calpain, inhibits this activity. In the present communication, we demonstrate that leupeptin and another calpain inhibitor, E64d, inhibit the fusion of mouse skeletal muscle C2C12 myoblasts to form multinucleated myotubes in tissue culture.
Cell Mol Biol (Noisy-le-grand)
PMID:The effect of protease inhibitors, leupeptin and E64d, on differentiation of C2C12 myoblasts in tissue culture. 148 17

In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies. The main focus of this study is the classification of individual EF-hand domains. Five subfamilies--calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin--and three uniques--call, squidulin, and calcium-dependent protein kinase--are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC. The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways.
J Mol Evol 1992 May
PMID:Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories. 160 95

One of the consequences of increased intracellular calcium in response to a variety of physiological stimuli is the calcium activation of cytosolic proteases. Unlike lysosomal proteases with broad specificity, these calcium-activated neutral proteases show limited proteolysis of a restricted set of substrate proteins suggesting they may play a regulatory role in cellular physiology. In this study we show that the neural cell adhesion molecules NCAM-180 and N-cadherin are substrates for such endogenous calcium-activated neutral proteases. In contrast, a third neural cell adhesion molecule G4/L1 was not susceptible to calcium-activated proteolysis. The threshold for activation of NCAM and N-cadherin proteolysis is in the micromolar range of calcium suggesting that NCAM and N-cadherin are substrates for a mu-type calpain (calpain I). The site recognized by this protease is within intracellular domains of NCAM-180 and N-cadherin which are important for their interaction with cytoskeletal components. These results suggest that calcium-activated proteolysis at these sites in vivo could disrupt the linkage between extracellular ligand binding to these adhesion molecules and the normal intracellular effectors of such extracellular binding events.
Brain Res Mol Brain Res 1991 Aug
PMID:Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin. 166 41

Calpains and calpastatin in the brain of the rabbit were examined in experimental situations that could mimic some features of brain ischemia. Incubations of bisected brains in saline at 39 degrees C for 0.5, 1, or 1.5 h resulted in a decreased calpain I activity in the cytosol and in an increased hydrophobicity of cytosolic calpain II activity. Incubation of brain homogenates at different pH levels demonstrated an almost-complete transfer of calpains from the cytoplasmic compartment to the membranes when pH was lowered from 6 to 5. At pH values lower than 5, the total calpain activity (soluble plus membrane-bound) markedly decreased. No significant changes of calpastatin activity or its subcellular distribution was found following incubation of the homogenates at different pH levels.
Mol Chem Neuropathol 1991 Apr
PMID:Changes in brain calpain activity as a result of in vitro ischemia and pH alterations. 191 Mar 62

The relationships among 153 EF-hand (calcium-modulated) proteins of known amino acid sequence were determined using the method of maximum parsimony. These proteins can be ordered into 12 distinct subfamilies--calmodulin, troponin C, essential light chain of myosin, regulatory light chain, sarcoplasmic calcium binding protein, calpain, aequorin, Stronglyocentrotus purpuratus ectodermal protein, calbindin 28 kd, parvalbumin, alpha-actinin, and S100/intestinal calcium-binding protein. Eight individual proteins--calcineurin B from Bos, troponin C from Astacus, calcium vector protein from Branchiostoma, caltractin from Chlamydomonas, cell-division-cycle 31 gene product from Saccharomyces, 10-kd calcium-binding protein from Tetrahymena, LPS1 eight-domain protein from Lytechinus, and calcium-binding protein from Streptomyces--are tentatively identified as unique; that is, each may be the sole representative of another subfamily. We present dendrograms showing the relationships among the subfamilies and uniques as well as dendrograms showing relationships within each subfamily. The EF-hand proteins have been characterized from a broad range of organismal sources, and they have an enormous range of function. This is reflected in the complexity of the dendrograms. At this time we urge caution in assigning a simple scheme of gene duplications to account for the evolution of the 600 EF-hand domains of known sequence.
J Mol Evol 1990 Jun
PMID:Evolution of EF-hand calcium-modulated proteins. I. Relationships based on amino acid sequences. 211 31

Membrane phospholipid asymmetry is considered to be a general property of biological membranes. Detailed information is presently available on the non-random orientation of phospholipids in red cell- and platelet membranes. The outer leaflet of the lipid bilayer membrane is rich in choline-phospholipids, whereas amino-phospholipids are abundant in the inner leaflet. Studies with blood platelets have shown that these asymmetries are not maintained when the cells are activated in various ways. Undoing the normal asymmetry of membrane phospholipids in activated blood cells is presumably mediated by increased transbilayer movement of phospholipids. This process, which leads to increased exposure of negatively charged phosphatidylserine at the outer surface, plays an important physiological role in local blood clotting reactions. A similar phenomenon occurs in sickled red cells. Phospholipid vesicles breaking off from reversibly sickled cells contribute similarly to intravascular clotting in the crisis phase of sickle cell disease. The loss of membrane phospholipid asymmetry in activated platelets seem to be strictly correlated with degradation of cytoskeletal proteins by endogenous calpain. It is remarkable that membrane phospholipid asymmetry can be (partly) restored when activated platelets are treated with reducing agents. This leads to disappearance of phosphatidylserine from the outer leaflet where it was previously exposed during cell activation. These observations will be discussed in relation to two mechanisms which have been recognized to play a role in the regulation of membrane phospholipid asymmetry; i.e. the interaction of amino-phospholipids to cytoskeletal proteins, and the involvement of a phospholpid-translocase catalyzing outward-inward transbilayer movement of amino-phospholipids.
Mol Cell Biochem
PMID:Loss of membrane phospholipid asymmetry during activation of blood platelets and sickled red cells; mechanisms and physiological significance. 269 31

Troponin has been prepared from the asynchronous flight muscle of Lethocerus (water bug) taking special care to prevent proteolysis. The regulatory complex contained tropomyosin and troponin components. The troponin components were Tn-C (18,000 Mr), Tn-T (apparent Mr 53,000) and a heavy component, Tn-H (apparent Mr 80,000). The troponin was tightly bound to tropomyosin and could not be dissociated from it in non-denaturing conditions. A complex of Tn-T, Tn-H and tropomyosin inhibited actomyosin ATPase activity and the inhibition was relieved by Tn-C from vertebrate striated muscle in the presence of Ca2+. However, unlike vertebrate Tn-I, Tn-H by itself was not inhibitory. Monoclonal antibodies were obtained to Tn-T and Tn-H. Antibody to Tn-T was used to screen an expression library of Drosophila cDNA cloned in lambda phage. The sequence of cDNA coding for the protein was determined and hence the amino acid sequence. The Drosophila protein has a sequence similar to that of vertebrate skeletal and cardiac Tn-T. The sequence extends beyond the carboxyl end of the vertebrate sequences, and the last 40 residues are acidic. Part of the sequence of Drosophila Tn-T is homologous to the carboxyl end of the Drosophila myosin light chain MLC-2 and one anti-Tn-T antibody cross-reacted with the light chain. Lethocerus Tn-H is related to the large tropomyosins of Drosophila flight muscle, for which the amino acid sequence is known, since antibodies that recognize this component also recognize the large tropomyosins. Tn-H is easily digested by calpain, suggesting that part of the molecule has an extended configuration. Electron micrographs of negatively stained specimens showed that Lethocerus thin filaments have projections at about 39 nm intervals, which are not seen on thin filaments from vertebrate striated muscle and are probably due to the relatively large troponin complex. Decoration of the thin filaments with myosin subfragment-1 in rigor conditions appeared not to be affected by the troponin. The troponin of asynchronous flight muscle lacks the Tn-I component of vertebrate striated muscle. Tn-H occurs only in the flight muscle and may be involved in the activation of this muscle by stretch.
J Mol Biol 1988 Dec 05
PMID:Troponin of asynchronous flight muscle. 285 58

The increasing effect of regucalcin, isolated from rat liver cytosol, on neutral proteolytic activity in the hepatic cytosol was characterized. The proteolytic activity was markedly elevated by the addition of regucalcin (0.1-0.5 microM) in the absence of Ca2+. This increase was not significantly altered by the presence of diisopropylfluorophosphate (DPF; 2.5 mM)--although DFP caused a significant decrease in the proteolytic activity. Regucalcin (0.25 microM) additively enhanced the dithiothreitol (DTT; 1.0 mM)--increased proteolytic activity, while the regucalcin or DTT effect was completely abolished by NEM (5 mM), indicating that regucalcin may act on the SH group in proteases. Also, regucalcin (0.25 microM) enhanced the effect of Ca2+ (10 microM) increasing liver proteolytic activity, suggesting that regucalcin does not influence on the active sites for Ca2+ in proteases. Moreover, the proteolytic activity of regucalcin (0.25 microM) was significantly decreased by the presence of calpastatin (24 micrograms/ml), an inhibitor of Ca(2+)-activated neutral protease (calpain). Now, regucalcin (0.25 microM) increased about 7-fold the activity of m-calpain isolated from rabbit skeletal muscle. These observations demonstrate that regucalcin directly activates cysteinyl-proteases. Regucalcin may have a role as a potent proteolytic activator in the cytoplasm of liver cells.
Mol Cell Biochem 1995 Jul 05
PMID:Characterization of regucalcin effect on proteolytic activity in rat liver cytosol: relation to cysteinyl-proteases. 747 35

Tests were carried out to determine if repetitive bursts of afferent stimulation activate calpain, a calcium-dependent protease hypothesized to be involved in the production of long-term potentiation. Antibodies against a stable breakdown product that results from proteolysis of spectrin by calpain were used to identify sites of enzyme activation in cultured hippocampal slices. Slices in which theta-burst stimulation was applied to the Schaffer collateral fibers had pronounced accumulations of breakdown product that were restricted to field CA1, the zone innervated by the stimulated axons. Labelling occurred in the form of scattered puncta and was also present in dendritic processes. The extent of these effects was correlated (r = 0.73) with the amount of theta-burst stimulation delivered. Control slices or those receiving low frequency stimulation had variable, but uniformly lower, amounts of breakdown product and were clearly distinguishable from those given theta bursts. Statistical analyses using a six point rating scheme confirmed this point (P < 0.001). These results satisfy an essential prediction of the hypothesis that calpain plays an important role in the induction of long-term potentiation.
Brain Res Mol Brain Res 1995 Aug
PMID:Proteolysis of spectrin by calpain accompanies theta-burst stimulation in cultured hippocampal slices. 749 60


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