""""""""In collaboration with Richard Furlanetto, University of Rochester, we have used the LexA based yeast two-hybrid system to identify binding partners for the IGF-I receptor. Proteins which bind to the IGF-I receptor are candidates for being involved in signaling by the IGF-I receptor. SOCS-2 (suppressor of cytokine signaling-2) was cloned by utilizing the insulin-like growth factor I receptor (IGF-IR) cytoplasmic domain as bait in a yeast two-hybrid screen of a human fetal brain library. The SOCS-2 protein interacted strongly with the autophosphorylated IGF-IR and not with a kinase negative mutant receptor in the two-hybrid assay. Mutation of receptor tyrosines 950, 1250, 1251, and 1316 to phenylalanine or deletion of the COOH-terminal 93 amino acids did not result in decreased interaction of the receptor with SOCS-2 protein, suggesting that tyrosines in the kinase domain of the receptor may be important for the interaction of the SH2 domain of SOCS-2 with the receptor. SOCS-1 protein also interacted with the activated receptor in the two-hybrid assay. Glutathione S-transferase-SOCS-2 associated with activated IGF-IR in lysates of mouse fibroblasts overexpressing IGF-IR. Human embryonic kidney cells (293) were transiently transfected with vectors containing IGF-IR and FLAG epitope-tagged SOCS-2. After IGF-I stimulation, activated IGF-IR was found in anti FLAG immunoprecipitates and, conversely, FLAG-SOCS-2 was found in anti IGF-IR immunoprecipitates. Thus, SOCS-2 interacted with IGF-I R both in vitro and in vivo. SOCS-2 mRNA was expressed in many human fetal and adult tissues with particularly high abundance in fetal kidney and adult heart, skeletal muscle, pancreas, and liver. Several members of the SOCS family had previously been shown to be negative regulators of cytokine receptor signaling via the JAK/STAT pathway. Our results raise the possibility that SOCS proteins may also play a role in IGF-I receptor signaling.""""""""
| Jackson-Booth, P-G; Terry, C; Lackey, B et al. (2003) Inhibition of the biologic response to insulin-like growth factor I in MCF-7 breast cancer cells by a new monoclonal antibody to the insulin-like growth factor-I receptor. The importance of receptor down-regulation. Horm Metab Res 35:850-6 |
| Spence, Susan L; Dey, Bhakta R; Terry, Cheryl et al. (2003) Interaction of 14-3-3 proteins with the insulin-like growth factor I receptor (IGFIR): evidence for a role of 14-3-3 proteins in IGFIR signaling. Biochem Biophys Res Commun 312:1060-6 |
