Role of phosphorylation of the cytoplasmic domain of the alpha(2)-macroglobulin receptor (LRP).
The low density lipoprotein receptor-related protein (alpha(2)MR/LRP) is a cell surface receptor which is present on most cells and tissues. We show that the 85 kDa subunit, containing the transmembrane region and cytoplasmic domain is phosphorylated in vivo. Comparison of the phosphorylation of the low density lipoprotein receptor (LDLR) with a chimeric receptor containing the cytoplasmic domain of the alpha(2)MR/LRP (LDLR/LRP) showed that phosphorylation is exclusive to the cytoplasmic domain. Staurosporine, a general kinase inhibitor, resulted in a 40% lowering of phosphorylation of LDLR/LRP, but did not give rise to measurable changes in its membrane traffic in MDCK cells. The role of phosphorylation on degradation of the receptor was studied using inhibitors of lysosomal and proteasomal degradation. These studies showed that LDLR/LRP was rapidly turned over by proteasomal degradation but that this turnover was also not a consequence of phosphorylation.
Djordjevic
J T
JT
Centre for Immunology, University of New South Wales, Darlinghurst, NSW, 2010, Australia.
Waterkeyn
J G
JG
Hennessy
K L
KL
Stanley
K K
KK
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012867:Skin / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D000511:alpha-Macroglobulins; D019311:Staurosporine