Autolysis of Calcium-Activated Neutral Protease of Chicken Skeletal Muscle1

Suzuki, Koichi; Tsuji, S.; Ishiura, Shoichi; Kimura, Yoshinobu; Kubota, Shunichiro; Imahori, Kazutomo

doi:10.1093/oxfordjournals.jbchem.a133656

Cited by 129 publications

(64 citation statements)

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“…It was discovered in 1981 that m-calpain autolyzes rapidly in the presence of Ca 2ϩ (439,440), and it is now known that both -and m-calpain autolyze when incubated with Ca 2ϩ (62,81,101,373,376). Although it is not uncommon for proteolytic enzymes to autolyze, autolysis of the calpains has several unique features (autoproteolysis may be grammatically more accurate than autolysis, but the briefer autolysis will be used here with the understanding that the autolytic events are proteolytic).…”

Section: Autolysis and The Proenzyme Questionmentioning

confidence: 99%

The Calpain System

Goll

Thompson

et al. 2003

Physiological Reviews

2,568

2,801

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Goll, Darrel E., Valery F. Thompson, Hongqi Li, Wei Wei, and Jinyang Cong. The Calpain System. Physiol Rev 83: 731–801, 2003; 10.1152/physrev.00029.2002.—The calpain system originally comprised three molecules: two Ca2+-dependent proteases, μ-calpain and m-calpain, and a third polypeptide, calpastatin, whose only known function is to inhibit the two calpains. Both μ- and m-calpain are heterodimers containing an identical 28-kDa subunit and an 80-kDa subunit that shares 55–65% sequence homology between the two proteases. The crystallographic structure of m-calpain reveals six “domains” in the 80-kDa subunit: 1) a 19-amino acid NH2-terminal sequence; 2) and 3) two domains that constitute the active site, IIa and IIb; 4) domain III; 5) an 18-amino acid extended sequence linking domain III to domain IV; and 6) domain IV, which resembles the penta EF-hand family of polypeptides. The single calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent. Since 1989, cDNA cloning has identified 12 additional mRNAs in mammals that encode polypeptides homologous to domains IIa and IIb of the 80-kDa subunit of μ- and m-calpain, and calpain-like mRNAs have been identified in other organisms. The molecules encoded by these mRNAs have not been isolated, so little is known about their properties. How calpain activity is regulated in cells is still unclear, but the calpains ostensibly participate in a variety of cellular processes including remodeling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis. Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage in response to events such as myocardial infarcts, stroke, and brain trauma.

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Section: Autolysis and The Proenzyme Questionmentioning

confidence: 99%

The Calpain System

Goll

Thompson

et al. 2003

Physiological Reviews

2,568

2,801

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“…Several different modes of regulation have been identified, although their contributions in vivo have not yet been determined. The large subunits of some calpains are autolyzed on activation, which removes domain I and abolishes the N-terminal link between the large and small subunits, thereby allowing movement of domain II (Baki et al, 1996;Cong et al, 1989;Elce et al, 1997;Guttmann et al, 1997;Imajoh et al, 1986;Molinari et al, 1994;Suzuki and Sorimachi, 1998;Suzuki et al, 1981a). The truncated large subunit is catalytically active and has a lower requirement for calcium (Baki et al, 1996;Imajoh et al, 1986;Suzuki and Sorimachi, 1998;Suzuki et al, 1981b).…”

Section: Calpain Regulationmentioning

confidence: 99%

Regulating cell migration: calpains make the cut

Franco

Huttenlocher

2005

Journal of Cell Science

437

406

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The calpain family of proteases has been implicated in cellular processes such as apoptosis, proliferation and cell migration. Calpains are involved in several key aspects of migration, including: adhesion and spreading; detachment of the rear; integrin- and growth-factor-mediated signaling; and membrane protrusion. Our understanding of how calpains are activated and regulated during cell migration has increased as studies have identified roles for calcium and phospholipid binding, autolysis, phosphorylation and inhibition by calpastatin in the modulation of calpain activity. Knockout and knockdown approaches have also contributed significantly to our knowledge of calpain biology, particularly with respect to the specific functions of different calpain isoforms. The mechanisms by which calpain-mediated proteolysis of individual substrates contributes to cell motility have begun to be addressed, and these efforts have revealed roles for proteolysis of specific substrates in integrin activation, adhesion complex turnover and membrane protrusion dynamics. Understanding these mechanisms should provide avenues for novel therapeutic strategies to treat pathological processes such as tumor metastasis and chronic inflammatory disease.

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“…To confirm that calpastatin contains the XL region in vivo, a polyclonal antisera was prepared against a 17-amino acid peptide from the XL region (amino acids [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. This antisera recognized only the 145-kDa band in the crude ammonium sulfate fraction (Fig.…”

Section: Isolation Of Full-length Bovinementioning

confidence: 99%

The Bovine Calpastatin Gene Promoter and a New N-terminal Region of the Protein Are Targets for cAMP-dependent Protein Kinase Activity

Cong¹,

Thompson²,

Goll³

et al. 1998

Journal of Biological Chemistry

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To investigate the regulation of calpastatin gene expression, we isolated bovine heart calpastatin cDNAs and 5-regions of the calpastatin gene. Analysis of 5-cDNA sequence identified a new translation initiation site that is in frame and 204 nucleotides upstream of the previously designated start site. Conceptual translation from this upstream AUG produces a protein containing 68 additional N-terminal amino acids. This "XL" region contains three potential PKA phosphorylation sites but shares no homology with other regions of calpastatin or with any known protein. Immunoblot studies demonstrated that heart and liver contain a calpastatin protein of 145 kDa on SDS-polyacrylamide gel electrophoresis that comigrates with full-length bacterially expressed calpastatin and calpastatin produced by coupled in vitro transcription-translation from the upstream AUG. An antibody raised against the XL region recognized the 145-kDa band, demonstrating that the upstream AUG is utilized and that the 145-kDa band represents full-length calpastatin in vivo. Transient transfection assays demonstrated that sequence within 272 nucleotides upstream of transcription initiation of the calpastatin gene is sufficient to direct moderate level transcription. Promoter sequences further upstream act to inhibit or stimulate transcriptional activity. Exposure of transfected cells to dibutyryl cAMP resulted in a 7-20-fold increase in promoter activity for constructs containing at least 272 nucleotides of upstream promoter sequence. Deletion analysis indicates that at least one cAMP-responsive element resides within 102 nucleotides of transcription initiation.

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Autolysis of Calcium-Activated Neutral Protease of Chicken Skeletal Muscle1

Cited by 129 publications

References 0 publications

The Calpain System

The Calpain System

Regulating cell migration: calpains make the cut

The Bovine Calpastatin Gene Promoter and a New N-terminal Region of the Protein Are Targets for cAMP-dependent Protein Kinase Activity

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