The colony-stimulating factor 1 receptor: pleiotropy of signal-response coupling.

Abstract

The colony-stimulating factor 1 receptor (CSF-1R) is a cell surface glycoprotein consisting of an extracellular ligand-binding domain, a single membrane-spanning segment, and an intracellular tyrosine kinase domain. Binding of CSF-1 activates the receptor kinase, leading to "autophosphorylation" of receptor subunits and the concomitant phosphorylation of a series of cellular proteins on tyrosine residues. The diverse effects of CSF-1 on mononuclear phagocyte proliferation, differentiation, survival, and macrophage effector function appear to reflect the ability of CSF-1R to simultaneously modulate the activities of a series of intracellular proteins that function in relaying biochemical signals. Sequences surrounding sites of ligand-induced tyrosine phosphorylation within CSF-1R may serve as targets for interactions with cellular effector proteins whose activities are modified by receptor binding, tyrosine phosphorylation, or both. The specificity of the cellular response to CSF-1 may depend, at least in part, on the differential coupling of the receptor to these "downstream" effectors in different cell types.