NF2 in Hrs-Mediated Signal Transduction
Annual rept. 1 Oct 2001-1Oct 2002
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. 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 Regulated overexpression of HRS in rat schwannoma cells results in similar effects as overexpression of schwannomin. This includes growth inhibition, decreased motility and abnormalities in cell spreading Gutmann et al. 2001. 2 A recently emerging function for Hrs is the sorting of endosomes containing EGR-receptor. We have begun to examine this effect in RT4 cells overexpressing Hrs or schwannomin. 3 We have begun to generate mouse embryonic fibroblast cell lines that express schwannomin or HRS under the control of the tet-regulatable promotor.
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