title: Increased membrane-associated phorbol-12,13 dibutyrate (PDBu) receptor function in sickle red cells.
abstract: A four-fold increase in the binding of 3H-PDBu by red cell membrane ghosts isolated from sickle red cells compared to that from normal controls is presented. Phosphorylation studies with gamma-32P-ATP indicate a similar (two to three-fold) increase in the radiolabelling of the acid-precipitable membrane proteins in sickle red cells. When red cells were loaded with Ca2+ using Ionophore A23187, both normal and sickle red cells enhanced their phosphorylation and sickle red cells to a greater extent than normal red cells. Polyacrylamide slab gel electrophoretic separation of the phosphoproteins and autoradiography also reveal phosphorylation, predominantly of protein bands 3, 4.1 and 4.9 which are known in the red cells as specific substrates for the PDBu receptor, protein kinase C. These results indicate that membrane association of protein kinase C in sickle red cells is increased, possibly as a consequence of the pathological change in their ability to accumulate intracellular calcium.
mesh_terms: D000755:Anemia, Sickle Cell / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002352:Carrier Proteins; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D011493:Protein Kinase C / Q000097:blood*; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000097:blood*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D010703:Phorbol Esters; D010750:Phosphoproteins; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D011493:Protein Kinase C; D002118:Calcium