Nickel inhibits binding of alpha2-macroglobulin-methylamine to the low-density lipoprotein receptor-related protein/alpha2-macroglobulin receptor but not the alpha2-macroglobulin signaling receptor.
A previous study demonstrated that activated alpha2-macroglobulin (alpha2M*) binding to the low-density receptor-related protein/alpha2-macroglobulin receptor (LRP/alpha2MR) 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 alpha2M molecule upstream of the carboxyl terminal receptor recognition domain. This observation is consistent with previous observations from this laboratory suggesting that alpha2M* binding to LRP/alpha2MR involves a region of the alpha2M 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 alpha2M* or a cloned and expressed receptor binding fragment (RBF) to the recently described alpha2M signaling receptor as assessed by direct binding and signal transduction studies.
Odom
A R
AR
Department of Pathology, The Duke University Medical Center, Durham, North Carolina 27710, USA.
Misra
U K
UK
Pizzo
S V
SV
D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000378:metabolism; D008744:Methylamines; D051379:Mice; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008744:Methylamines; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D009532:Nickel; C027451:methylamine