Nickel inhibits binding of alpha(2)-macroglobulin-methylamine to the low-density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor but not the alpha(2)-macroglobulin signaling receptor

A previous study demonstrated that activated alpha/(2)-macroglobulin (alpha/M-2*) binding to the low-density receptor-related protein/alpha 2 macroglobulin receptor (LRP/alpha(2)MR) is blocked by Ni2+ [Hussain, M. M,, et al. (1995) Biochemistry 34, 16074-16081], We now report that the effect of Ni2+ is on a region of the alpha(2)M molecule upstream of the carboxyl terminal receptor recognition domain. This observation is consistent with previous observations from this laboratory suggesting that alpha(2)M* binding to LRP/alpha(2)MR involves a region of the alpha(2)M molecule immediately upstream of the receptor recognition domain [Enghild, J, J., et al. (1989) Biochemistry 28, 1406-1412]. We further demonstrate that Ni2+ has no effect on the binding of alpha(2)M* or a cloned and expressed receptor binding fragment (RBF) to the recently described alpha(2)M Signaling receptor as assessed by direct binding and signal transduction studie.