Control of receptor function The availability of cytokines and growth factors is controlled by their expression. There are multiple ways to regulate receptor function:(i) expression of receptors may be restricted to specific cell types;(ii) the receptor number on the plasma membrane may vary due to receptor mRNA regulation or receptor internalization, leading to either degradation or recycling;(iii) the receptor affinities may be modulated on some cells by additional membrane proteins, which interact with the ligand-binding protein; or (iv) the membrane-bound receptor may be trans-formed into a soluble form by limited proteolysis (shedding). Interestingly, there is a second important biochemical pathway leading to the generation of soluble receptors: soluble receptors can be translated from differentially spliced mRNAs lacking transmembrane and cytoplasmic regions. To date, many soluble forms ofmembrane-bound cytokine and growth-factor receptors, which have retained their ability to specifically bind their ligands, have been identified in biological fluids and biochemically characterized.

It should be noted that not only cytokines and growth factors have soluble counterparts of their receptors, but so also do other transmembrane proteins such as adhesion molecules (eg ICAM-1/CD54)(Seth et al., 1991), the transferrin receptor (Chitambar et al., 1991), thereceptor for complexes between lipopoly-saccharide (LPS) and LPS-binding protein (CD14)(Landmann et al., 1992), the low-affinity receptor for IgE (CD23)(Alderson et al., 1992), and the membrane glycoproteins CD27and CD40 expressed on B-and T-cells (Loenen et al., 1992). In this review we will discuss the present knowledge about soluble cytokine and growth-factor receptors with emphasis on biochemical mechanisms involved in the generation and physio-logical actions of these molecules. Until now few reviews on this subject have been published (Fernandez-Botran, 1991; Tedder, 1991). We have not reviewed the many studies carried out on the regulation of the soluble interleukin (IL)-2 receptor in various disease states.