Characteristics of soluble and membrane-bound forms of haemopoietic growth factor receptors: relationships to...

In order to understand how extracellular growth factors (colony-stimulating factors, CSFs) induce biological responses in haemopoietic cells it is necessary first to describe the primary binding characteristics of isolated receptors and then to determine how living cells modify these binding characteristics and process the ligand-receptor complexes. We have solubilized multi-CSF (interleukin 3) and granulocyte macrophage CSF (GM-CSF) receptors in 1% Triton X-100 and developed methods to study their binding characteristics in solution. Whilst the multi-CSF receptor exhibits the same binding characteristics in solution and in the cellular state, the GM-CSF receptor appears to be converted to a lower affinity form in solution. In intact cells at biological temperatures both types of receptor and ligand are internalized and degraded under steady-state conditions; the kinetic processes underlying the maintenance of the steady state are characteristic for each type of receptor and each type of cell. We have determined the kinetic constants for a variety of CSFs and cell types and correlated steady-state receptor occupancy with biological responses. The importance of CSF utilization rate by responsive cells has also been evaluated as a mechanism for limiting biological responses.