title: Actin filament associated protein mediates c-Src related SRE/AP-1 transcriptional activation.
abstract: AFAP is an adaptor protein involved in cytoskeletal organization and intracellular signaling. AFAP binds and activates c-Src; however, the downstream signals of this interaction remain unknown. Here we show that co-expression of AFAP and c-Src induce transcriptional activation of SRE and AP-1 in a c-Src activity dependent fashion. Structural-functional studies suggest that the proline-rich motif in the N-terminus of AFAP is critical for c-Src activation, and subsequent SRE/AP-1 transactivation and the actin-binding domain in the AFAP C-terminus is negatively involved in the regulation of AFAP/c-Src mediated SRE/AP-1 transactivation. Selective deletion of this domain enhances transactivation of SRE. We conclude that in addition to its role in the regulation of cytoskeletal structures, AFAP may also be involved in the c-Src related transcriptional activities.
authors.affiliation: Division of Cellular and Molecular Biology, University Health Network Toronto General Research Institute, Toronto, Ontario, Canada.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Helan
authors.initials: H
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Monika
authors.initials: M
authors.lastname: Lodyga
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Bai
authors.forename: Tianru
authors.initials: T
authors.lastname: Jin
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D019556:COS Cells; D002645:Chickens; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D018909:src Homology Domains; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C497360:AFAP1 protein, human; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; C502774:SRE protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D019061:src-Family Kinases