title: SRChing for the substrates of Src.
abstract: By the mid 1980's, it was clear that the transforming activity of oncogenic Src was linked to the activity of its tyrosine kinase domain and attention turned to identifying substrates, the putative next level of control in the pathway to transformation. Among the first to recognize the potential of phosphotyrosine-specific antibodies, Parsons and colleagues launched a risky shotgun-based approach that led ultimately to the cDNA cloning and functional characterization of many of today's best-known Src substrates (for example, p85-Cortactin, p110-AFAP1, p130Cas, p125FAK and p120-catenin). Two decades and over 6000 citations later, the original goals of the project may be seen as secondary to the enormous impact of these protein substrates in many areas of biology. At the request of the editors, this review is not restricted to the current status of the substrates, but reflects also on the anatomy of the project itself and some of the challenges and decisions encountered along the way.
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Reynolds
authors.affiliation: Arrowhead Research Corporation, Madison, WI, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Kanner
authors.affiliation: Departments of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Bouton
authors.affiliation: Department of Biochemistry, 3124 HSN, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Schaller
authors.affiliation: Department of Neurobiology and Anatomy, 1833 Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Weed
authors.affiliation: Department of Medical Lab Sciences, College of Health Sciences, University of Delaware, Newark, DE, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Flynn
authors.affiliation: Departments of Microbiology, Immunology and Cancer Biology, University of Virginia Cancer Center, Charlottesville, VA, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Parsons
mesh_terms: D000818:Animals; D051177:Catenins / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D051356:Cortactin / Q000502:physiology; D050719:Crk-Associated Substrate Protein / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D020543:Proteome; D019061:src-Family Kinases / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: C497360:AFAP1 protein, human; C493841:BCAR1 protein, human; C495868:CTTN protein, human; D051177:Catenins; D051356:Cortactin; D050719:Crk-Associated Substrate Protein; D008840:Microfilament Proteins; D020543:Proteome; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D000095002:Delta Catenin