Adaptor Molecules of Intracellular Signal Transduction

The occurrence of multiple protein modules is characteristic for adaptor proteins these mediate different protein-protein interactions and can thus bring about crosslinking of signal proteins. 

The function of many adaptor proteins is closely linked with the cell membrane or with the cytoskeleton. The occurrence of PH domains and myristoyl modifications suggests that adaptor proteins are involved in particular in coordination and assembly of signal complexes on the iimer side of the ceU membrane. 

Adaptor proteins are, above aU, important elements for controlling the subceUular organization of Tyr and Ser phosphorylation events. Thus, many adaptor proteins contain PTB or SH2 domains that direct specific interactions with autophosphorylation sites on an activated receptor. 

The Crk protein was first discovered as the transforming principle of the retroviruses CTIO and ASV-1. Abl tyrosine kinase is under discussion as a binding partner of the SH3 domain of Crk (Feller et al., 1994). Possible binding partners of the SH2 domain have been described but their physiological function is unclear. 

The insulin receptor substrate IRS couples the insulin receptor to sequential effector molecules (review Ogawa et al., 1998). On binding of insulin to the insulin receptor, the tyrosine kinase activity of the receptor is stimulated. The IRS protein is phosphory-lated at several Tyr residues, which then serve as attachment points for sequential effector molecules as e.g. the Grb2-mSos complex, the P13-kinase and the protein tyrosine phosphatase SHP-2. The IRS protein also has a phosphotyrosine binding domain and a PH domain. Both modules are required for signal transduction in vivo. It is assumed that the PTB domain binds to autophosphorylation sites of the insulin receptor and that the PH domain is involved in membrane association of IRS. 

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