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 Grfo2 in the cytoplasm of unstimulated cells. Following a 1-min stimulation with CSF-1, p120^c-cbl becomes tyrosine-phosphorylated and associates with tyrosine-phosphorylated Shc 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 Shc 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.