Ghosh, Madhumita; Shanker, Sreejesh; Siwanowicz, Igor; Mann, Karlheinz; Machleidt, Werner; Holak, Tad A.
Proteolysis of insulin-like growth factor binding proteins (IGFBPs) by calpain.
In: Biological Chemistry, Vol. 386, No. 1: pp. 85-93
Calpains are non-lysosomal, Ca2+-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.