Sci. STKE, 27 March 2001
Receptor Biology Differential Galactosylation
Signal regulatory proteins (SIRPs) are transmembrane proteins with extensively glycosylated extracellular domains. SIRPs are expressed by neurons and myeloid cells and are regulators of receptor tyrosine kinases, as well as mediators of cell-cell adhesion, possibly through interactions with the integrin-associated protein CD47/IAP. Analysis of SIRPα from spleen and brain or from cultured cells of similar type (NR8383 myeloid cells and PC-12 neuronal cells) showed that the myeloid protein is approximately 112 kD and the brain form is approximately 85 kD and that the myeloid form contains substantially more galactose. This difference in galactose in SIRPα correlates with the difference in the activity of galactosyltransferase in these tissues and cells. To test the functional consequence of this difference in glycosylation, a soluble fusion protein of the extracellular domain of SIRPα and the Fc portion of human IgG was produced in normal or galactosylation-defective Chinese hamster ovary (CHO) cells. These two different glycoforms were then used to test for differences in binding to rat cerebellum and lymph node tissue sections and isolated cells. The staining patterns for the two glycoforms were not identical in the lymph node. The galactose-deficient form bound with higher avidity to isolated lymphocytes. Furthermore, the proteins that coimmunoprecipitated from NR8383 cells treated with either of the two soluble glycoforms showed several differences, suggesting that the differential glycosylation may regulate the ligand specificity of SIRPα.
I. M. van den Nieuwenhof, C. Renardel de Lavalette, N. Diaz, I. van Die, T. K. van den Berg, Differential galactosylation of neuronal and haematopoietic signal regulatory protein-α determines it cellular binding-specificity. J. Cell Sci. 114, 1321-1329 (2001). [Online Journal]
Citation: Differential Galactosylation. Sci. STKE 2001, tw11 (2001).
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