SHC proteins (SHC 1, 2, 3) are signalling adapters, able to interact with phosphorylated Y496 of TRKA. SHC2 and SHC3 appear to be the primary SHC adaptor proteins in neurons as they are expressed in both the developing and adult nervous system. SHC1 is expressed embryonically but not in the adult brain, whereas SHC3 expression is lower in the embryonic brain and increases post-natally. Pi-Y496 of TrkA can also be bound by FRS2. The competitive binding between Frs2 and SHC at this phospho-tyrosine residue contributes to a cellular switch between cell cycle progression (SHC recruitment) and cell cycle arrest/differentiation (Frs2 recruitment).
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