A previous study demonstrated that activated
2-macroglobulin (
2M*) binding to thelow-density receptor-related protein/
2-macroglobulin receptor(LRP/
2MR) is blocked by Ni
2+[Hussain, M.M., et al. (1995)
Biochemistry 34,16074-16081]. We now report that the effect ofNi
2+ is on a regionof the
2M molecule upstream of the carboxyl terminalreceptor recognition domain. This observationis consistent with previous observations from this laboratorysuggesting that
2M* binding toLRP/
2MRinvolves a region of the
2M molecule immediatelyupstream of the receptor recognition domain [Enghild,J. J., et al. (1989)
Biochemistry 28,1406-1412]. We further demonstrate that Ni
2+ hasno effect on thebinding of
2M* or a cloned and expressed receptorbinding fragment (RBF) to the recently described
2M signaling receptor as assessed by direct binding andsignal transduction studies.