References 1 Cosman D, Lyman SD, Idzerda RL et al. A new cytokine receptor superfamily. TIBS 1990; 15:265-270. 2 Kaushansky K, Karplus PA. Hematopoietic growth factors: Understanding functional diversity in structural terms. Blood 1993;82:3229-3240. 3 Walter MR, Cook WJ, Zhao BG et al. Crystal structure of recombinant human interleukin-4. J Biol Chem 1992;267:2037 1-20376. 4 De Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: Crystal structure of the complex. Science 1992;255:306. 5 Kruse N, Shen B-J, Arnold S et al. Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation.We: have entertained the hypothesis that red cells not only function as gas transporters but may also assist with the physiological functions of other blood cells. When platelets are activated, local concentrations of thrombin, platelet-derived growth factor, and ADP increase. We have found that each of these can induce a rapid and dramatic diminution in the phosphorylation of red cell membrane proteins: p spectrin, adducin and protein 4.1. Since these skeletal proteins together with actin form the junctional complex, and because dephosphorylation of junctional complex proteins strengthens their interactions within the membrane skeleton, the net effect of the platelet stimulants on red cell properties should be to rigidify the cell. We speculate that this rigidification might aid in retaining the stimulated red cells in the hemostatic plug. While the signaling pathways leading to these changes in membrane protein phosphorylation are not yet worked out, activation of phosphotidylinositol-specific phospholipase C appears to be one component.Red cells may also respond to activated neutrophils. We have found that the H 2 0 2 released by activated neutrophils stimulates a red cell tyrosine kinase that phosphorylates band 3 on tyrosines 8 and 21 (See Figure). These two tyrosines are located in the middle of a glycolytic enzyme binding site on band 3, and their phosphorylation is shown to block this enzyme binding. Because the reversible binding of the enzymes to band 3 leads to their reversible inhibition, phosphorylation of band 3 in vivo results in an elevation of RBC glycolysis. A similar elevation of the pentose phosphate pathway is also observed. Evidence will be presented that the soluble protein tyrosine kinases, p72Eyk and LYN, are responsible for phosphorylation of band 3 in red cells, and that ~7 2 "~ actually binds to band 3 via a novel SH2 domain. The structure of this novel SH2 domain will be described, and its role in red cell signal transduction will be discussed.
References1 Low PS, Allen DP, Zioncheck TF et al. Tyrosine phosphorylation of band 3 inhibits peripheral protein binding. J Biol Chem 1987;262:4592-4596. 2 Low PS, Geahlen RL, Mehler E et al. Extracellular control of erythrocyte metabolism mediated by a cytoplasmic tyrosine kinase. Biomed Biochim Acta 1990;49: 135-140. 3 Harrison ML, Rathinavelu P, ...
