Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.54 (calpain 3)
 430 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoiesis is tightly controlled by a family of cytokines that signal through a related set of receptors. The pleiotropic and overlapping response of a cell to different cytokines is reflected in the number and complex pattern of activated signal transducers. Of special interest is STAT5, which is stimulated by a large and diverse set of cytokines. In addition to the two highly homologous proteins, STAT5A and STAT5B, encoded by duplicated genes, expression and activation of a dominant-negative, carboxyl-truncated form has also been described in early hematopoietic progenitors. We show here that a protease expressed in early hematopoietic cells cleaves the alpha forms of STAT5A/5B (p96/p94) to generate carboxyl-truncated beta forms (p80/p77). Inhibition studies assigned this protease to the serine class of endopeptidases. Cell fractionation experiments showed that the protease is associated with the nucleus in a constitutively activated form and does not require an activated STAT5 substrate. The ability of a protease to modulate the specificity of an activated transcription factor is unprecedented and underlines the importance of proteases in regulation of cell functions.
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PMID:Carboxyl-truncated STAT5beta is generated by a nucleus-associated serine protease in early hematopoietic progenitors. 949 Jun 72

Babesia bigemina infection of mature bovine erythrocytes results in new proteins specifically exposed on the parasitized cell surface. Monoclonal antibody (MAb) 64/32 binds a protein, designated p94, on B. bigemina-infected erythrocytes but not on either uninfected or B. bovis-parasitized erythrocytes. However, p94 was not encoded by B. bigemina and was not a parasite-modified erythrocyte membrane protein. In contrast, we showed that p94 could be eluted from the infected erythrocyte surface and was identified as specifically bound immunoglobulin M (IgM) heavy chain for the following reasons: (i) MAb 64/32 bound a reduced molecule of 94 kDa in both infected erythrocyte lysates and normal bovine serum; (ii) MAb 64/32 bound a 94-kDa molecule in reduced preparations of purified IgM; (iii) an anti-bovine mu heavy-chain MAb, BIg73, reacted specifically with the surface of infected erythrocytes and bound the 94-kDa molecule in lysates of infected erythrocytes, normal bovine serum, and purified IgM; and (iv) immunoprecipitation of infected erythrocyte lysates with MAb 64/32 depleted the 94-kDa antigen bound by anti-mu MAb BIg73 and vice versa. Binding of IgM to the infected erythrocyte surface was detected in vivo early in acute parasitemia and occurred during both the trophozoite and merozoite stages of intraerythrocytic parasitism. The common feature of IgM binding to the parasitized erythrocyte surface among otherwise genetically and antigenically distinct B. bigemina strains is suggestive of an advantageous role in parasite survival in vivo.
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PMID:In vivo binding of immunoglobulin M to the surfaces of Babesia bigemina-infected erythrocytes. 959 68

The objective of this study was to determine whether the improvements in growth and efficiency of gain achieved by recombinant porcine somatotropin (pST) are associated with altered expression of the p94, calpastatin, or alpha-actin genes in porcine longissimus (LD) muscle. Forty-eight barrows (initial 64.2 to 67.4 kg BW) were assigned to four treatments (n = 12) arranged as a 2 x 2 factorial in a randomized complete block design. Factors were duration of treatment (3 or 6 wk) and pST administration (0 or 3 mg x pig(-1) x d(-1)). Plasma samples were obtained 24 h after the first pST injection and at the end of the each treatment period for assays of selected variables. The LD samples were obtained at 3 and 6 wk of pST treatment. Northern blot analysis of calpastatin expression in LD muscle revealed three distinct transcription products of approximately 8.5 (CPST I), 5.5 (CPST II), and 2.5 (CPST III) kb; CPST II was reduced (P < .02) 33 and 61% by pST at 3 and 6 wk, respectively, whereas CPST I and III were not influenced (P > .12). Neither alpha-actin nor p94 was responsive to pST injection. As expected, pST resulted in higher (50%, P < .02) plasma insulin within 24 h and one- and twofold higher (P < .01) concentrations at 3 and 6 wk, respectively. Glucose was increased (P < .01) at 3 (15%) and 6 (10%) wk, whereas urea nitrogen was reduced (32 to 36%, P < .01). The efficacy of pST was evident in that ADG was improved (P < .01) 11 to 13% independent of time. Likewise, feed intake was reduced (P < .01) 10 to 11% and gain: feed improved (P < .01) approximately 26% for pigs receiving pST independent of time. These data indicate that the enhanced muscle growth achieved by pST is not associated with altered expression of p94 or alpha-actin, or an increase in the abundance of any calpastatin transcription product.
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PMID:Porcine somatotropin improves growth in finishing pigs without altering calpain 3 (p94) or alpha-actin mRNA abundance and has a differential effect on calpastatin transcription products. 962 45

p94 (calpain3), a muscle-specific member of the calpain family, has been shown to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A), a form of autosomal recessive and progressive neuromuscular disorder. To elucidate the molecular mechanism of LGMD2A, we constructed nine p94 missense point mutants found in LGMD2A and analyzed their p94 unique properties. All mutants completely or almost completely lose the proteolytic activity against a potential substrate, fodrin. However, some of the mutants still possess autolytic activity and/or connectin/titin binding ability, indicating these properties are not necessary for the LGMD2A phenotypes. These results provide strong evidence that LGMD2A results from the loss of proteolysis of substrates by p94, suggesting a novel molecular mechanism leading to muscular dystrophies.
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PMID:Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A. 964 72

Recent studies indicate that calpain, a cytosolic Ca2+-dependent protease, constitutes a large family comprising ubiquitous, tissue-specific, and atypical calpains. p94 is a homologue of the catalytic large subunit of calpain, expressed predominantly in skeletal muscle. Recently, p94 has been found to interact with connectin/titin, a muscle elastic protein, and its gene has been identified as being responsible for limb-girdle muscular dystrophy type 2A. The loss of function of a calpain species eventually leads to the activation of proteases including other calpain species responsible for muscle degradation. p94 does not form a complex with the small subunit of calpain (30K), but exists as a homodimer. This, together with other results, led us to consider a novel mechanism for the activation of calpain, a Ca2+-induced subunit rearrangement.
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PMID:Skeletal muscle-specific calpain, p49: structure and physiological function. 976 16

Six isolates of Mycoplasma bovoculi obtained from cattle herds with bovine keratoconjunctivitis were analyzed by gel electrophoresis and immunoblotting techniques. All six strains showed similarity in their protein profiles although no two patterns were identical. Antigenic differences between strains were detected in immunoblots reacted with post-exposure calf serum. A common 94 kDa protein band designated p94 was detected in all six strains reacted with monoclonal antibody MA25.5 developed to one of the strains. The p94 was also recognized in these strains by the calf serum. Trypsin treatment of intact mycoplasma cells resulted in the removal of p94 from immunoblots reacted with MA or hyperimmune rabbit serum. Other trypsin-resistant antigens shared between strains or being strain-specific in nature were identified when trypsin-treated mycoplasma cells were reacted with hyperimmune rabbit serum. The p94 antigen was shown to be of mycoplasmal origin by radio-immunoprecipitation using the MA or hyperimmune rabbit serum. These studies identify the presence of a surface antigen (p94) on M. bovoculi membrane in all strains examined that is trypsin sensitive by the use of monoclonal antibody, calf serum and hyperimmune rabbit serum.
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PMID:Identification and localization of a 94 kDa membrane protein found in Mycoplasma bovoculi strains. 977 58

p94, a skeletal muscle-specific calpain, has attracted much attention because its gene is responsible for limb-girdle muscular dystrophy type 2A. p94, however, has not been characterized at the protein and enzyme levels, owing to its very rapid autolysis. In the present study, a purification procedure for p94 was first established by using a recombinant inactive p94 expressed in COS cells in which the active site cysteine residue was changed to serine [p94(C129S)]. The isolation of native p94 from rabbit skeletal muscle by the established method with conventional procedures was extremely difficult because p94 became highly unstable in a crude extract on the addition of NaCl for separation. Purification of native p94 was possible with an antibody-affinity column but only as an inactive enzyme; p94(C129S) was purified as a homodimer. Characterization of p94, especially autolysis, was performed with partly purified native p94 and p94(C129S). The autolysis of p94, which consisted at least partly of an intermolecular reaction, proceeded in three consecutive steps; 60 and 58 kDa fragments were produced as intermediates before a stable 55 kDa fragment appeared. Autolysis of p94 was regarded as a degradative step rather than for the activation of the enzyme. All the autolysis cleavage sites were located in the p94-specific insertion sequence 1 region, which explains why p94 is unstable compared with the other calpains. The autolysis sites in p94 clearly showed a different specificity relative to the autolytic and proteolytic cleavage sites of the ubiquitous mu- and m-calpains, in its preference for residues at the P3 to P1' sites, indicating a distinct substrate specificity and function for the muscle enzyme.
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PMID:Purification of native p94, a muscle-specific calpain, and characterization of its autolysis. 979 99

The t(11;14)(q13;q32) and its molecular counterpart, bcl1/JH, are characteristic of mantle-cell lymphomas (MCL). Molecular detection of the translocation is useful in diagnosis and classification, and also shows promise in detecting minimal residual disease. The purpose of this study was to determine the frequency of detecting bcl1/JH by polymerase chain reaction (PCR) compared with Southern blot analysis in cases proven by cytogenetic analysis to harbor t(11;14). Southern blot analysis using two probes targeting the major translocation cluster (MTC) and a third probe targeting the p94 region was performed, along with PCR using two different bcl1 MTC primers, on 18 cases of MCL known to have t(11;14). Southern blot analysis revealed bcl1 rearrangement in 13 of 18 cases (72%), 12 with MTC breakpoints and 1 with a p94 breakpoint. The 2.1-kb MTC probe "b" was superior to the smaller 700-bp probe "a" in detecting these rearrangements. The MTC translocation was identified by PCR in 10 of 12 cases, and both primer sets that were tested performed equally well. This study illustrates the frequency with which molecular methods detect known t(11;14) translocations in MCLs. These results may help clinical laboratory scientists optimize their procedure for detecting bcl1 translocations by molecular methods at initial diagnosis and for purposes of detecting minimal residual disease.
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PMID:Molecular methods for detecting t(11;14) translocations in mantle-cell lymphomas. 991 31

Tenderization of skeletal muscle in meat animals has been closely linked to the postmortem activity of the calpain proteolytic enzyme system, which includes the specific inhibitor calpastatin. Increased understanding of the skeletal muscle-specific calpain isoform p94 has prompted suggestions as to whether it too could have a role in the tenderization process. In this study, two groups of pigs were identified in which shear force measurements after 8 d of conditioning indicated a large variation in the tenderness of longissimus muscle. The quantity of p94 in the muscle was monitored by immunoblotting, using a porcine-specific polyclonal antibody raised against a recombinant peptide fragment generated as a fusion protein. The antiserum recognized a 94-kDa protein associated with myofibrils in skeletal but not cardiac muscle, as expected for this calpain isoform, although it could not be tested with the native protein because of the extreme instability of p94. In the first experiment, the mean shear force for the tough group was 6.71 +/- .28 kg (n = 12, SEM) and that of the tender group was 3.87 +/- .12 kg (n = 12), but there was no difference in the normalized absorbance of the immunopositive 94 kDa band on Western blots from samples collected at approximately 40 min postmortem. In the second experiment, the stability of p94 in chilled carcasses was investigated over 24 h, using a further two groups of 10 tough and 10 tender pigs of mean shear force values 5.36 +/- .14 kg and 2.81 +/- .15 kg, respectively. In tough and tender animals, there was a decline (P < .05) in the 94-kDa immunostaining material of mean half-lives of 13.8 and 12.9 h, respectively, although there was considerable variability. Despite this variability in half lives and shear force values, no correlation was seen between these factors. Thus, in porcine longissimus muscle, the variability in tenderness after 8 d of conditioning cannot be attributed to an underlying variability in p94.
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PMID:Relationship between skeletal muscle-specific calpain and tenderness of conditioned porcine longissimus muscle. 1022 62

The genome of the nucleopolyhedrovirus (NPV) (T3 strain) pathogenic for Bombyx mori (Bm) was sequenced and analysed. The BmNPV genome was 128,413 nucleotides long with a G+C content of 40% and contained 136 open reading frames (ORFs) encoding predicted proteins of over 60 amino acids. Although phenotypically different, the genome organizations of BmNPV and Autographa californica multinucleocapsid NPV (AcMNPV) were closely related. The BmNPV genome was over 90% identical to about three-quarters of the genome of AcMNPV. The relatedness of predicted amino acid sequences of corresponding ORFs between BmNPV and AcMNPV was about 90%. However, the BmNPV genome lacked homologues of the following AcMNPV ORFs: Ac3 (conotoxin), Ac7 (orf603), Ac48 (etm), Ac49 (pcna), Ac70 (hcf-1), Ac86 (pnk/pnl) and Ac134 (p94). In addition, BmNPV contained five ORFs related to Ac2. A high frequency of multiple 3 bp insertions was also found within BmNPV and AcMNPV coding sequences.
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PMID:Sequence analysis of the genome of Bombyx mori nucleopolyhedrovirus. 1035 80


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