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HGS is involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. It could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. HGS may concentrate ubiquitinated receptors within clathrin-coated regions. It is involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM. This complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. HGS may contribute to the efficient recruitment of SMADs to the activin receptor complex.
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