Yeast two-hybrid studies show that the C-terminal tail of the somatostatin2A (sst2A) receptor binds to cortactin-binding protein i (CortBPi; Zitzer et al. i999b) also termed proline rich synapse associated protein, ProSAPi (Boeckers et al. i999) or Shank2. CortBPi is a PDZ-containing protein that binds to the SH3 domain of cortactin, an actin-binding protein involved in the restructuring of the cortical actin cytoskeleton. The C-terminal tail of the sst2A receptor binds to the PDZ domain of CortBPi that in turn binds to cortactin and forms a scaffold between the receptors and the cytoskeleton. Coexpression of both proteins results in a redistribution of CortBPi to the cell membrane that is enhanced when cells are treated with somatostatin receptor inducing factor (SRIF) suggesting that agonist activation of the receptor increases the accessibility of the C-terminal domain for the CortBPi PDZ domain. Using the same approach as above a human somatostatin receptor interacting protein (SSTRIP), a protein that has strong homology with the rat protein Shanki/Synamon was also shown to interact with sst2A (Zitzer et al. i999a). In addition, the ssti receptor was shown to interact with the human homologue of Skbi (SkbiHs; Schwarzler et al. 2000) and while the function of SkbiHs is not fully understood the interaction required the full C-terminal sequence of ssti. In addition, cotransfection of both proteins in HEK cells resulted in a higher number of binding sites for SRIF suggesting that SkbiHs may aid in targeting the ssti receptor to the cell surface (Schwarzler etal. 2000). Thus CortBPi, SSTRIP, and SkbiHs define a novel family of multidomain proteins containing a PDZ domain, ankyrin repeats, SH3 binding regions and a SAM domain, and are involved in the targeting and localization of somatostatin receptors to the plasma membrane.

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