Proteolysis of insulin-like growth factor binding proteins (IGFBPs) by calpain.
Calpains are non-lysosomal, Ca 2+ -dependent cysteine proteases, which are ubiquitously distributed across cell types and vertebrate species. The rules that govern calpain specificity have not yet been determined. To elucidate the cleavage pattern of calpains, we carried out calpain-induced proteolytic studies on the insulin-like growth factor binding proteins IGFBP-4 and -5. Proteolysis of IGFBPs is well characterized in numerous reports. Our results show that calpain cleavage sites are in the non-conserved unstructured regions of the IGFBPs. Compilation of the calpain-induced proteolytic cleavage sites in several proteins reported in the literature, together with our present study, has not revealed clear preferences for amino acid sequences. We therefore conclude that calpains seem not to recognize amino acid sequences, but instead cleave with low sequence specificity at unstructured or solvent-exposed fragments that connect folded, stable domains of target proteins.
Ghosh
Madhumita
M
Max Planck Institute for Biochemistry, D-82152 Martinsried, Germany.
Shanker
Sreejesh
S
Siwanowicz
Igor
I
Mann
Karlheinz
K
Machleidt
Werner
W
Holak
Tad A
TA
D000595:Amino Acid Sequence; D002154:Calpain / Q000737:chemistry*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity / Q000502:physiology
D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D002154:Calpain; C449002:mu-calpain