Glycoprotein signal transduction

Some cytokine receptors are composed of a single transmembrane polypeptide (e.g. receptors for IL-8, -9 and -10). Many contain two polypeptide components (including the IL-3, -4, and -5 receptors), and a few contain three or more polypeptide components (e.g. the IL-2 receptor contains three polypeptide chains). In some instances a single cytokine may be capable of initiating signal transduction by binding two or more distinct receptors (e.g. IL-1 has two distinct receptors (types I and II), both of which are transmembrane glycoproteins). 

The IFN-y receptor (the type II receptor) displays a more limited cellular distribution than that of the type I receptors (Table 8.5). This receptor is a transmembrane glycoprotein of molecular mass 50 kDa, which appears to function as a homodimer. The extracellular IFN-y binding region consists of approximately 200 amino acid residues folded into two homologous domains. Initiation of signal transduction also requires the presence of a second transmembrane glycoprotein known as AF-1 (accessory factor 1), which associates with the extracellular region of the receptor. 

The intact GM-CSF receptor is a heterodimer, consisting of a low-affinity a-chain and a P-chain, which also forms part of the IL-3 and IL-5 receptors. (The P-chain alone does not bind GM-CSF.) The a-chain is an 80 kDa glycoprotein and exhibits only a short intracellular domain. The larger P-chain (130 kDa) displays a significant intracellular domain. Signal transduction involves the (tyrosine) phosphorylation of a number of cytoplasmic proteins (Figure 10.2). 

Brummendorf, T. and Rathjen, F. G. Axonal glycoproteins with immunoglobulin and fibronectin type II-related domains in vertebrates Structural features, binding activities and signal transduction. /. Neurochem. 61 1207-1219, 1993. 

TPO induces its characteristic effects by binding to a specific TPO receptor present on the surface of sensitive cells. The receptor, also known as c-mpl, is a single chain, 610 amino acid transmembrane glycoprotein. The mechanism of signal transduction triggered upon TPO-binding remains to be elucidated. 

Greenwalt D. E., Lipsky R. H., Ockenhouse C. F., Ikeda H., Tandon N. N. and Jamieson G. A. (1992) Membrane glycoprotein CD36 a review of its roles in adherence, signal transduction, and transfusion medicine. Blood 80, 1105-1115. 

Li, Y., Hua, F., Carraway, K.L., and Carothers Carraway, C.A. 1999. The pl85" -contain-ing glycoprotein complex of a microfilament-associated signal transduction particle. Purification, reconstitution, and molecular associations with p58 and actin. J Biol Chem 274(36) 25651-25658. 

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