Red cell membrane protein phosphorylation in hemolytic anemias and muscular dystrophies

We review our current understanding of membrane phosphorylation in normal and abnormal erythrocytes. The major phosphoproteins in red blood cell (RBC) membranes are spectrin (band 2), bands 3, 2.1, and 4.5, and glycophorin A. At least two protein kinases can be distinguished on the basis of their stimulation by cyclic AMP and salt; they are present both in the membrane and in the cytosol. Analysis of the conflicting data on endogenous membrane-protein phosphorylation in abnormal RBCs indicates a considerable variability of phosphorylation rates which largely depends on the manner of preparation of ghosts and enzyme assay conditions. This variability reflects differences in the partitioning of protein kinases between the membrane and cytosol, the specificity and accessibility of membrane-protein substrates, and reaction kinetics. We select examples of data from several hemolytic anemias to illustrate that precautions are needed to interpret abnormalities of membrane-protein phosphorylation properly; we discuss possible new methodological approaches.