Grb2 protein

The structure of the mSos protein (m=mammalian) is shown in Fig. 9.8. Sequence comparison with known Ras-specific GEFs has identified a common domain of ca.200 amino acids, to which nucleotide exchange activity has been assigned. Within this domain, three highly conserved sequence elements can be differentiated, separated by more variable sections. Other structural elements include a PH domain and a Pro-rich binding domain. The Pro-rich sequence fimctions as an attachment site for the SH3 group of Grb2 protein. 

The complex of Grb2 and mSos proteins forms a link between Ras protein and activated receptor tyrosine kinases. The Grb2 protein has two SH2 domains (see 8.5) and a SH3 domain. 

In the other pathway, an additional adaptor protein, the She protein (see 8.5), is involved in the signal transduction. The She protein has a phosphotyrosine binding domain (PTB domain) and specifically binds via this domain to autophosphorylated receptors such as the PDGF receptor and the EGF receptor. The She protein is phos-phorylated itself in the process. The phosphotyrosine residues may also serve as attachment points for the SH2 domain of Grb2 protein, whereby the Grb2-Sos complex is attached to the membrane. 

BRGAl, p53-BPl, NBSl, MDGl, (s.c. RAD9 s.p. Grb2) Protein-protein interactions for complex formation, and subnuclear localization Specific interaction domains include the BRGT domain and the FHA domain Adaptor/mediator... 

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