HIGH EXPRESSION OF INHIBITORY RECEPTOR SHPS-1 AND ITS ASSOCIATION WITH PROTEIN-TYROSINE-PHOSPHATASE SHP-1 IN MACROPHAGES

SHPS-1 (or SIRP) is a member of the immunoglobulin (Ig) superfamily ab undantly expressed in neurons and other cell types, Within its cytopla smic domain, it possesses at least two immunoreceptor tyrosine-based i nhibitory motifs, which are targets for tyrosine phosphorylation and m ediate the recruitment of SHP-2, an Src homology 2 (SH2) domain-contai ning protein-tyrosine phosphatase. Since other immunoreceptor tyrosine based inhibitory motifs-containing receptors have critical roles in t he negative regulation of hemopoietic cell functions, we wanted to exa mine the expression of SHPS-1 in cells of hematological lineages. By a nalyzing a panel of hemopoietic cell lines, evidence was provided that SHPS-1 is abundantly expressed in macrophages and, to a lesser extent , in myeloid cells. No expression was detected in T-cell or B-cell lin es. Expression of SHPS-1 could also be documented in normal ex vivo pe ritoneal macrophages. Further studies showed that SHPS-1 was an effici ent tyrosine phosphorylation substrate in macrophages. However, unlike in non-hemopoietic cells, tyrosine-phosphorylated SHPS-1 in macrophag es associated primarily with SHP-1 and not SHP-2, Finally, our analyse s allowed us to identify several isoforms of SHPS-1 in mouse cells. In part, this heterogeneity was due to differential glycosylation of SHP S-1, Additionally, it was caused by the production of at least two dis tinct shps-1 transcripts, coding for SHPS-1 polypeptides having differ ent numbers of Ig-like domains in the extracellular region, Taken toge ther, these findings indicate that SHPS-1 is likely to play a signific ant role in macrophages, at least partially as a consequence of its ca pacity to recruit SHP-1.