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 behavior of p120(c-cbl) in mouse BAC1.2F5 macrophages were investigated. p120(c-cbl) is associated with Grb2 in the cytoplasm of unstimulated cells. Following a 1-min stimulation with CSF-1, p120(c-cbl) be comes tyrosine-phosphorylated and associates with tyrosine-phosphorylated She and an unknown phosphotyrosyl protein (pp80). Simultaneously, it is ubiquitinated 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 association of p120(c-cbl) with She persists for at least 60 min. These data indicate that signaling via the CSF-1R involves the transient modification of p120(c-cbl) and its recruitment as a complex to membrane.