NF2 in Hrs-Mediated Signal Transduction
Annual rept. 11 Oct 1999-1 Oct 2000
CEDARS-SINAI MEDICAL CENTER LOS ANGELESCA
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We have identified Hrs hepatocyte growth factor-regulated tyrosine kinase substrate as an NF2 binding protein using the yeast two-hybrid system. Hrs is also known to interact with STAM signal transduction adaptor molecule which in turn interacts with JakSTAT kinases. Hrs appears to have growth suppressing functions at least in part mediated via binding to STAM with a resulting reduction in DNA synthesis. Progress is discussed in order of the three specific aims that were proposed originally 1 Using yeast two-hybrid and in vitro binding assays we have will fine-mapped the binding domains in Hrs, schwannomin, and STAM see Scoles et al., 2000. 2 We have determined the cellular distribution of schwannomin and Hrs in normal Schwann cells. We have determined that endogenous as well as exogenous schwannomin and Hrs colocalize in cell lines. We have completed the co-localization studies in cultured cells Scoles et al., 2000. Studies in tumors are in progress. 3 We have begun to generate cell lines that express schwannomin or HRS under the control of the tet-regulatable promoter. These lines will be used to examine the effects of overexpression of either protein on proliferation and STAT signaling.
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