The Role of the SPRY domain in the SPRY domain-containing SOCS box proteins

© 2005 Seth L. Masters.There are four mammalian SSB proteins (SSB-1 to -4), and these are characterized by a C-terminal SOCS box and central SPRY domain. The C-terminal SOCS box was first observed in proteins that were found to act as Suppressors of Cytokine Signalling and function by virtue of their SH2 domain. Other families containing the SOCS box motif were defined by the domains N-terminal to this, such as the ASBs (Ankyrin repeats), WSBs (WD40 repeats) and of course the SSBs (SPRY domains). This thesis describes a very broad investigation of the SSBs, a protein family about which very little was known. To begin with, functional investigation into the evolution of this family and analysis of murine SSB expression patterns was performed. This highlighted that the family was highly conserved and had differential expression in the mouse, suggestive of important, unique functional roles for the individual family members. The majority of work in the thesis then proceeds in three directions; (i) analysis of the SSB proteins in vivo, with genetic deletion of SSB-2 in the mouse, (ii) biochemically, with analysis of SSB binding partners, and (iii) structurally, with functional analysis of the structure of SSB-2