title: FAT1 cadherin is multiply phosphorylated on its ectodomain but phosphorylation is not catalysed by the four-jointed homologue.
abstract: The interaction between the Drosophila cadherins fat and dachsous is regulated by phosphorylation of their respective ectodomains, a process catalysed by the atypical kinase four-jointed. Given that many signalling functions are conserved between Drosophila and vertebrate Fat cadherins, we sought to determine whether ectodomain phosphorylation is conserved in FAT1 cadherin, and also whether FJX1, the vertebrate orthologue of four-jointed, was involved in such phosphorylation events. Potential Fj consensus phosphorylation motifs were identified in FAT1 and biochemical experiments revealed the presence of phosphoserine and phosphothreonine residues in its extracellular domain. However, silencing FJX1 did not influence the levels of FAT1 ectodomain phosphorylation, indicating that other mechanisms are likely responsible.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: Elham
authors.initials: E
authors.lastname: Sadeqzadeh
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Charles E
authors.initials: CE
authors.lastname: de Bock
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: O'Donnell
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Timofeeva
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Burns
authors.affiliation: Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; School of Environmental & Life Sciences, University of Newcastle, Ourimbah, NSW 2258, Australia. Electronic address: Rick.Thorne@newcastle.edu.au.
authors.forename: Rick F
authors.initials: RF
authors.lastname: Thorne
mesh_terms: D020816:Amino Acid Motifs; D055162:Biocatalysis; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary
chemical_list: D015820:Cadherins; C502403:FAT1 protein, human; C000592900:FJX1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins
keywords: Ectodomain phosphorylation; FAT1; FJX1; Fat cadherin; Four-jointed; Four-jointed box protein 1