title: Two novel Src homology 2 domain proteins interact to regulate dictyostelium gene expression during growth and early development.
abstract: There are 13 Dictyostelium Src homology 2 (SH2) domain proteins, almost 10-fold fewer than in mammals, and only three are functionally unassigned. One of these, LrrB, contains a novel combination of protein interaction domains: an SH2 domain and a leucine-rich repeat domain. Growth and early development appear normal in the mutant, but expression profiling reveals that three genes active at these stages are greatly underexpressed: the ttdA metallohydrolase, the abcG10 small molecule transporter, and the cinB esterase. In contrast, the multigene family encoding the lectin discoidin 1 is overexpressed in the disruptant strain. LrrB binds to 14-3-3 protein, and the level of binding is highest during growth and decreases during early development. Comparative tandem affinity purification tagging shows that LrrB also interacts, via its SH2 domain and in a tyrosine phosphorylation-dependent manner, with two novel proteins: CldA and CldB. Both of these proteins contain a Clu domain, a >200-amino acid sequence present within highly conserved eukaryotic proteins required for correct mitochondrial dispersal. A functional interaction of LrrB with CldA is supported by the fact that a cldA disruptant mutant also underexpresses ttdA, abcG10, and cinB. Significantly, CldA is itself one of the three functionally unassigned SH2 domain proteins. Thus, just as in metazoa, but on a vastly reduced numerical scale, an interacting network of SH2 domain proteins regulates specific Dictyostelium gene expression.
authors.affiliation: School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sugden
authors.forename: Susan
authors.initials: S
authors.lastname: Ross
authors.forename: Gareth
authors.initials: G
authors.lastname: Bloomfield
authors.forename: Alasdair
authors.initials: A
authors.lastname: Ivens
authors.forename: Jason
authors.initials: J
authors.lastname: Skelton
authors.forename: Annette
authors.initials: A
authors.lastname: Mueller-Taubenberger
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Williams
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D048948:14-3-3 Proteins; D015800:Protozoan Proteins; D014443:Tyrosine
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