title: Teaching an old dogma new tricks: twenty years of Shc adaptor signalling.
abstract: Shc (Src homology and collagen homology) proteins are considered prototypical signalling adaptors in mammalian cells. Consisting of four unique members, ShcA, B, C and D, and multiple splice isoforms, the family is represented in nearly every cell type in the body, where it engages in an array of fundamental processes to transduce environmental stimuli. Two decades of investigation have begun to illuminate the mechanisms of the flagship ShcA protein, whereas much remains to be learned about the newest discovery, ShcD. It is clear, however, that the distinctive modular architecture of Shc proteins, their promiscuous phosphotyrosine-based interactions with a multitude of membrane receptors, involvement in central cascades including MAPK (mitogen-activated protein kinase) and Akt, and unconventional contributions to oxidative stress and apoptosis all require intricate regulation, and underlie diverse physiological function. From early cardiovascular development and neuronal differentiation to lifespan determination and tumorigenesis, Shc adaptors have proven to be more ubiquitous, versatile and dynamic than their structures alone suggest.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1.
authors.forename: Melanie K B
authors.initials: MK
authors.lastname: Wills
authors.forename: Nina
authors.initials: N
authors.lastname: Jones
mesh_terms: D000818:Animals; D017209:Apoptosis; D002320:Cardiovascular Physiological Phenomena; D005260:Female; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology; D009376:Neoplasms, Hormone-Dependent / Q000503:physiopathology; D009424:Nervous System Physiological Phenomena; D018384:Oxidative Stress; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology; D055765:Shc Signaling Adaptor Proteins / Q000737:chemistry* / Q000266:history / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D018909:src Homology Domains
chemical_list: D055765:Shc Signaling Adaptor Proteins; D020794:Receptor Protein-Tyrosine Kinases