Characterization of a new p94-like calpain form in human lymphocytes.
Human circulating PBMC (peripheral blood mononuclear cells) contain three calpain isoforms distinguishable on the basis of their chromatographic properties. Two of these proteases belong to the ubiquitous calpain subfamily, corresponding to the classical mu- and m-calpain forms. The third, which shows peculiar activating and regulatory properties, is an alternatively spliced calpain 3 (p94) form. This new calpain differs from calpain 3 in that it has lost IS1 insertion and exon 15, a lysine-rich sequence regarded as a nuclear translocation signal. PBMC p94-calpain undergoes activation and inactivation without the accumulation of a low-Ca2+-requiring form that is typical of the classical activation processes of mu- and m-calpain. Furthermore, it differs from the ubiquitous forms in that it displays a lower sensitivity to calpastatin. On the basis of these selective properties, it can be postulated that PBMC p94-calpain can be activated in response to specific stimuli that are not effective on the other calpain isoenzymes. The enzyme is preferentially expressed in B- and T-lymphocytes, whereas it is poorly expressed in natural killer cells and almost undetectable in polymorphonuclear cells. This distribution might reflect the specific function of this protease, which is preferentially present in cells devoted to the production of the humoral, rather than to the cellular, immune response.
De Tullio
Roberta
R
Department of Experimental Medicine, Biochemistry Section, and Excellence Center for Biomedical Research, University of Genova Viale Benedetto XV, 1, 16132 Genova, Italy.
Stifanese
Roberto
R
Salamino
Franca
F
Pontremoli
Sandro
S
Melloni
Edon
E
D002118:Calcium / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D003001:Cloning, Molecular; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology; D017422:Sequence Analysis, DNA
D015853:Cysteine Proteinase Inhibitors; D018076:DNA, Complementary; D007527:Isoenzymes; D007976:Leupeptins; D002154:Calpain; C078134:calpain p94; C032854:leupeptin; D002118:Calcium