Biological characterization of uncleavable plasma membrane-anchored human macrophage colony-stimulating factor.
The cell-surface form of human macrophage colony-stimulating factor (CSF-1(256), M-CSFalpha) is a plasma membrane-anchored transmembrane protein from which the soluble CSF-1 is released by ectodomain proteolytic cleavage. We have previously generated two forms of cell surface CSF-1 which failed to undergo the cleavage by deleting residues 161-165 or residues 159-165 in the extracellular juxtamembrane region (1). To determine the biologic significance of the ectodomain cleavage, we compared the biosynthesis and biologic activities of uncleavable mutant CSF-1 forms with those of the cleavable wild-type (WT) CSF-1. We found that the uncleavable CSF-1 forms were able to accumulate on cell surface at about threefold higher level than the cleavable WT CSF-1 did. We further demonstrated that the uncleavable plasma membrane-anchored forms of CSF-1 were biologically active in mediating the proliferation of CSF-1-dependent cells as well as the intercellular adhesion between CSF-1 receptor-bearing cells and CSF-1 expressing cells. Furthermore, the adhesive activity of uncleavable CSF-1 forms was about twofold stronger than that of WT CSF-1, which indicated that the ectodomain cleavage system plays an important role in regulating the biologic activities of membrane-anchored CSF-1.
Deng
P
P
Department of Pathology, Childrens Hospital of Los Angeles, Los Angeles, California 90027, USA.
Wang
Y L
YL
Shahbazian
V L
VL
Pattengale
P K
PK
D016475:3T3 Cells; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis* / Q000378:metabolism*; D051379:Mice
D016173:Macrophage Colony-Stimulating Factor