PLASMA-MEMBRANE CALCIUM-PUMP ISOFORM 4A HAS A LONGER CALMODULIN-BINDING DOMAIN THAN 4B

Alternate splicing of human plasma membrane calcium pump isoform 4 (hP MCA4) transcripts causes the expression of two variants, hPMCA4a and h PMCA4b, which have different downstream regulatory regions, Of the two , hPMCA4a has a lower affinity for calmodulin and a lower effective af finity for Ca2+ (Enyedi, A, Verma, A. K., Helm, R,, Adamo, H. P,, Filo teo, A. G,, Strehler, E, E,, and Penniston, J. T, (1994) J, Biol, Chem . 269, 41-43), Additional consequences of the alternate splice were st udied by analyzing the characteristics of constructs (expressed in COS -1 cells) containing different portions of the carboxyl terminus of hP MCA4a, Our results show striking differences in the structure of the c almodulin-binding and autoinhibitory domains of the two variants, The calmodulin-binding region of hPMCA4b is a region of about 28 residues, whereas that of hPMCA4a is about 49 residues long and is probably int errupted by a region not involved in the binding, The autoinhibitory r egion of hPMCA4b (a part of the downstream region that keeps the molec ule inactive in the absence of Ca2+-calmodulin) is divided between the 28-residue calmodulin-binding region and a downstream region, whereas in hPMCA4a, all of it is contained within the 49-residue calmodulin-b inding region.