THE 2 ISOTYPES OF THE HUMAN INSULIN-RECEPTOR (HIR-A AND HIR-B) FOLLOW DIFFERENT INTERNALIZATION KINETICS

Human insulin receptor (HIR) is expressed in two isoforms which differ in the C-terminal end of the α-subunit (HIR-A= -12 aa, HIR-B= +12 aa). We studied internalization kinetics of HIR-A and HIR-B in Rat1 fibroblasts. Internalized receptors were quantified by 125I-insulin binding after cell trypsinisation and solubilization, surface receptors were determined by 125I-insulin binding to intact cells and by chemical crosslinking with B26-125I-insulin. HIR-A and HIR-B show different kinetics of receptor internalization. While in HIR-A cells the maximum of internalization (approx. 65% of total) is reached after 10 min followed by a high recycling rate (approx. 80% of internalized receptors after 20 min), the internalization in HIR-B cells reaches a maximum (approx. 60% of total) after 15 min without detectable recycling within 30 min. The data show that the different α-subunits of both receptor types determine different velocities of internalization and determine whether a fast recycling occurs. © 1991.