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 p120c-cbl in mouse BAC1.2F5 macrophages were investigated. p120c-cbl is associated with Grb2 in the cytoplasm of unstimulated cells. Following a 1-min stimulation with CSF-1, p120c-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 p120c-cbl with Shc persists for at least 60 min. These data indicate that signaling via the CSF-1R involves the transient modification of p120c-cbl and its recruitment as a complex to membrane.
Department of Developmental, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Y
Y
Wang
Y G
YG
Yeung
W Y
WY
Langdon
E R
ER
Stanley
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D014443:Tyrosine / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D014452:Ubiquitins; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C493849:Cbl protein, mouse