C-CBL IS TRANSIENTLY TYROSINE-PHOSPHORYLATED, UBIQUITINATED, AND MEMBRANE-TARGETED FOLLOWING CSF-1 STIMULATION OF MACROPHAGES

Early colony stimulating factor-1 (CSF-1) induced changes in the behav ior of p120(c-cbl) in mouse BAC1.2F5 macrophages were investigated. p1 20(c-cbl) is associated with Grb2 in the cytoplasm of unstimulated cel ls. Following a 1-min stimulation with CSF-1, p120(c-cbl) be comes tyr osine-phosphorylated and associates with tyrosine-phosphorylated She a nd an unknown phosphotyrosyl protein (pp80). Simultaneously, it is ubi quitinated and translocated to the membrane. By 10 min of stimulation, this c-Cbl exhibits substantially decreased tyrosine phosphorylation and is de-ubiquitinated and relocated in the cytosol. However, the ass ociation of p120(c-cbl) with She persists for at least 60 min. These d ata indicate that signaling via the CSF-1R involves the transient modi fication of p120(c-cbl) and its recruitment as a complex to membrane.