A 22-kd protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain

Abstract

We have previously shown that at least five linked genes are co-amplified and overexpressed in the multi-drug resistant (MDR) Chinese hamster ovary cell line CHRC5. We show here that one of these genes (class 4) codes for a small phosphorylated, cytosolic protein, sorcin/V19, known to be overproduced by many MDR cell lines. The class 4 gene codes for a nested set of mRNAs, varying in size between 1000 and 2500 nucleotides. Sequence analysis of complementary DNAs shows that these mRNAs encode a protein of 198 amino acids. The identity of this protein with sorcin was established by comparison with the amino acid sequence of two peptides from mouse sorcin. Hamster sorcin is a 22-kd protein with four 'E-F hand' structures typical of calcium-binding sites and it has substantial homology with the light chain of calpain. Two of the calcium-binding sites contain putative recognition sites for cAMP-dependent protein kinase. These may account for the known phosphorylation of sorcin. The unknown function of sorcin might therefore be controlled by both calcium and cAMP levels. The contribution of sorcin to multidrug resistance, if any, remains to be tested.