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)

Previous genetic and physical studies of LGMD2A, an autosomal recessive form of limb-girdle muscular dystrophy, have led to the establishment of a 10-12 Mb YAC contig encompassing the morbid locus. In order to progress toward the identification of the gene involved in LGMD2A, a primary transcription map of this genomic region was generated. The direct cDNA selection strategy was used with three YACs covering the candidate region and two different muscle cDNA libraries. Seventeen transcription units were identified among 171 cDNA fragments analysed. Five sequences corresponded to known genes, and twelve to new ones. They were characterized for their sequences, physical positions within the YAC contig, and expression patterns. Among those specifically transcribed in muscle, the calpain gene is a good positional and functional candidate for LGMD2A.
Hum Mol Genet 1995 Apr
PMID:A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene. 763 22

N-terminal peptides from the calpain small subunit were shown to have dose-dependent chemotactic activity toward several types of leukemia cells: T cell, B cell, monocyte and granulocyte/monocyte line leukemia cells. In order to prove that chemotaxis is mediated via receptors, a fluorescein-labeled probe was prepared from one of the N-terminal peptides and its interaction with peripheral leukocytes was estimated by means of flow cytometry, resulting in staining not only of neutrophils but also of most of the monocytes and more than half of the T and B lymphocytes. The results indicate that calpain-derived N-terminal peptides may be involved in defense mechanisms, inducing chemotaxis of immunocytes as well as that of neutrophils.
Biochem Mol Biol Int 1995 Feb
PMID:Neutrophil chemotactic N-acetyl peptides from the calpain small subunit are also chemotactic for immunocytes. 766 78

Aurintricarboxylic acid (ATA) is an endonuclease inhibitor which has been shown to block apoptotic cell death. We have now demonstrated that ATA is also an inhibitor of the Ca(2+)-activated neutral protease (calpain), a class of cytosolic enzyme that may also be activated during apoptosis. The two major calpain isoforms (mu- and m-calpain) were both inhibited by ATA with IC50's of 22 microM and 10 microM, respectively. The autolysis of purified mu-calpain was prevented by ATA in a concentration-dependent manner. Using casein zymography, it was found that the inhibition of mu-calpain by ATA was reversible. Finally, in a fetal rat cerebrocortical culture model of excitotoxicity, pre- and post-treatment of ATA (50 microM) reduced N-methyl-D-aspartate (NMDA)-induced spectrin breakdown and neuronal death, while application of ATA concurrent to NMDA challenge alone had no effect. This pattern of protection could not be explained by simple NMDA receptor antagonism. We thus propose that the neuroprotective effect of ATA could be in part due to its ability to inhibit calpain.
Biochem Mol Biol Int 1995 Jun
PMID:Aurintricarboxylic acid is an inhibitor of mu- and m-calpain. 766 33

Calpains are calcium-dependent proteases believed to participate in calcium-regulated signal pathways in cells. Ubiquitous calpains as well as tissue-specific calpains have been found in vertebrates. We isolated cDNA clones for a highly tissue-specific calpain gene from Drosophila melanogaster, CalpA, at 56C-D on the second chromosome. The expression of the CalpA gene product was monitored by using a specific antiserum directed against the product expressed by one cDNA clone. The encoded protein is found in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. In the blood cell line mbn-2, calpain is associated with a granular component in the cytoplasm. The expression of this protein is more restricted than that of the corresponding transcripts, which are widely distributed in the central nervous system, digestive tract, and other tissues. The sequence of CalpA is closely related to that of vertebrate calpains, but an additional segment is inserted in the calmodulin-like carboxy-terminal domain. This insert contains a hydrophobic region that may be involved in membrane attachment of the enzyme. Differential splicing also gives rise to a minor transcript that lacks the calmodulin-like domain.
Mol Cell Biol 1995 Feb
PMID:CalpA, a Drosophila calpain homolog specifically expressed in a small set of nerve, midgut, and blood cells. 782 49

Phosphorylation of calpain II (or its inhibitor) by the catalytic subunit of cyclic AMP-dependent protein kinase (A-PK), cyclic GMP-dependent protein kinase (G-PK), and protein kinase C (PK-C) was analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. Among these protein kinases, the catalytic subunit of A-PK exhibited the strongest phosphorylations of both calpain II and its inhibitor. Arachidonic acid and staurosporine effectively inhibited phosphorylation regardless the type of kinase tested. Despite its lack of effect on the phosphorylation of calpain II by the catalytic subunit of A-PK, sphingosine moderately enhanced the phosphorylation of calpain II by G-PK. Other agents, including phosphatidylethanolamine, phosphatidylinositol and 1, 2-dioleoyl-sn-glycerol, had no significant effect.
Mol Cell Biochem 1994 Jul 27
PMID:Regulation of the phosphorylation of calpain II and its inhibitor. 784 69

Platelet actin binding protein (ABP) as isolated from human platelets exists in at least four phosphorylated forms which we have designated ABP-0, ABP-1, ABP-2, and ABP-3 whose phosphate content ranges from 18 (ABP-0) to 40 (ABP-3) moles Pi/mole ABP. These forms differ in their resistance to calpain cleavage and ability to cross-link F-actin with ABP-3 being the best in each of these properties. Attempts to phosphorylate ABP-1, two or three with protein kinase C (PKC) were unsuccessful except if the proteins were pretreated with Escherichia coli alkaline phosphatase. All of the forms could be phosphorylated with cAMP-dependent kinase (PKA) and subsequent resistance to calpain cleavage conferred. Phosphorylation/dephosphorylation of ABP may be an important regulatory mechanism by which the cytoskeletal architecture is stabilized or transformed.
Cell Mol Biol Res 1994
PMID:Existence of multiple phosphorylated forms of human platelet actin binding protein. 786 35

An alignment/phylogeny of the papain superfamily of cysteine proteases was created using an initial structure-based alignment followed by successive iterations of sequence alignment and phylogenetic inference. The iterative approach resulted in significant improvements in the alignment/phylogeny. There were three groups of cysteine proteases that were distantly related and which could be aligned against each other only in the active site regions: the papain group, which included such stereotypical cysteine proteases as cathepsins B, C, H, L and S; and the bleomycin hydrolase and calpain groups. There was one bacterial sequence in each of the bleomycin hydrolase and calpain groups. The former probably arose by lateral gene transfer, the latter possibly by direct evolution from an ancestral protease predating the eukaryote/prokaryote divergence. The phylogeny of the papain group indicated that many families diverged almost simultaneously early during eukaryotic evolution. In mammals there are at least 12 distinct families of cysteine proteases, possibly many more, including at least two as yet uncharacterized enzymes.
J Mol Biol 1995 Feb 17
PMID:Alignment/phylogeny of the papain superfamily of cysteine proteases. 786 79

The detailed localization of mRNAs for calpain II and calpastatin was examined in adult rat brain by in situ hybridization histochemistry. The expression patterns of the two mRNAs were similar to each other throughout the brain in terms of relative expression intensity, and almost all neurons expressed both mRNAs more or less. Among them, neurons in cranial nerve nuclei and some others in the brain stem expressed at relatively high levels, suggesting the high involvement of the non-lysosomal proteolytic system in the function of these neurons. On the other hand, the expression levels of the two mRNAs in non-neuronal cells including glia were basically low with the choroid plexuses expressing calpastatin mRNA relatively highly.
Brain Res Mol Brain Res 1994 Apr
PMID:Localization of mRNAs for calpain and calpastatin in the adult rat brain by in situ hybridization histochemistry. 802 82

Micromolar and millimolar Ca(2+)-requiring neutral protease (calpain I and calpain II) along with their endogenous inhibitor calpastatin were isolated and partially purified from the same preparation of rat intestinal epithelial cells. Calpain I and II were partially purified by 1300 and 900-fold with 57 and 53 per cent yield, respectively. The optimum assay conditions revealed pH 7.5, 20 min incubation at 25 degrees C and 0.24% casein substrate for both calpains. The optimum calcium concentration obtained for calpain I and II were 25 microM and 4 mM, respectively. Distribution of rat intestinal epithelial cells calpain I and II along with calpastatin during cell differentiation stages in weanling to senescence age were studied. Calpain I in weanling rats was in an increasing order from villus to crypt regions. Adult rats indicated well expressed consistent calpain I throughout the differentiation stages. Whereas, significant lowering towards crypt region cells were evident in old rats. Calpain II in weanling and adult rats was found to be consistent throughout the differentiation stages. Old animals revealed an increasing trend from villus to crypt region with insignificant activity present in upper villus cells. Concomitantly, different concentrations of calpastatin were observed throughout the differentiation stages in all the age groups. Moreover, the levels of calpains exceeded that of calpastatin in most of the epithelial cell populations during developmental stages. In addition to casein, intestinal epithelial cell membranes were found to be equally good substrates for calpains. Proteolytic susceptibility of weanling, adult and old rat membrane proteins varied significantly all along the ageing process in rats. Simultaneous age-dependent calpastatin response were also evident. Taken together the results obtained provided strong evidence that calpain plays significant role in rat intestinal cell differentiation and ageing process with calpastatin as its specific regulatory protein.
Mol Cell Biochem 1994 Feb 09
PMID:Calpain from rat intestinal epithelial cells: age-dependent dynamics during cell differentiation. 804 65

Apolipoprotein (apo) B is an obligatory component of triglyceride-rich lipoproteins. In the rare autosomal recessive disorder abetalipoproteinemia (ABL), no triglyceride-rich lipoproteins are secreted. Mutations in the gene encoding the 97-kDa subunit of a microsomal triglyceride transfer protein (MTP) cause ABL (Sharp, D., Blinderman, L., Combs, K. A., Klenzle, B., Ricci, B., Wager-Smith, K., Gil, C. M., Turck, C. W., Bouma, M. E., Rader, D. J., Aggerbeck, L. P., Gregg, R. E., Gordon, D. A., and Wetterau, J. R. (1993) Nature 365, 65-69; Shoulders, C. C., Brett, D. J., Bayliss, J. D., Narcisi, T. M., Jarmuz, A., Grantham, T. T., Leoni, P. R. D., Bhattacharya, S., Pease, R. J., Cullen, P. M., Levi, S., Byfield, P. G. H., Purkiss, P., and Scott, J. (1993) Hum. Mol. Genet. 2, 2109-2116). Here we have examined whether MTP is both necessary and sufficient to mediate the secretion of apoB-containing lipoproteins from cells that do not normally express either of these proteins. Carboxyl-terminal truncated forms of apoB, apoB17, and apoB41 on the centile system were expressed in COS-1 cells. ApoB17 was secreted whereas apoB41 was unable to traverse the secretory pathway. Cotransfection of apoB41 and MTP promoted the secretion of apoB41 as a buoyant lipoprotein particle with a modal density of 1.15 g/ml. When cotransfected COS-1 cells were cultured under conditions that increase the secretion of apoB100 from HepG2 cells, secretion of apoB41 was similarly increased. N-Acetyl-leucyl-leucyl-norleucinal (ALLN), a calpain I inhibitor, abolished intracellular degradation of apoB41 and increased secretion 2.5-fold. Oleate, a substrate for triglyceride synthesis, reduced degradation from 50 to 19% and increased secretion by 2.5-fold. The effects of ALLN and oleate were additive. We conclude that the secretion of apoB from COS-1 cells cotransfected with apoB and MTP is determined by the competitive processes of lipoprotein assembly and intracellular degradation in the endoplasmic reticulum and that MTP is the only tissue-specific component, other than apoB, required for the secretion of apoB-containing lipoproteins.
 ...
PMID:Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells. 807 15


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