Two novel Src homology 2 domain proteins interact to regulate Dictyostelium gene expression during growth and early development

Christopher Sugden, Susan Ross, Gareth Bloomfield, Alasdair Ivens, Jason Skelton, Annette Mueller-Taubenberger, Jeffrey G. Williams

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    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 under-expressed: the ttdA metallohydrolase, the abcG10 small molecule transporter, and the cinB esterase. In contrast, the multi-gene 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 under-expresses 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.

    Original languageEnglish
    Pages (from-to)22927-22935
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume285
    Issue number30
    DOIs
    Publication statusPublished - 23 Jul 2010

    Keywords

    • SH2 domain
    • Mitochondrial morphology
    • Discoideum
    • STAT
    • Pathway

    Cite this

    Sugden, C., Ross, S., Bloomfield, G., Ivens, A., Skelton, J., Mueller-Taubenberger, A., & Williams, J. G. (2010). Two novel Src homology 2 domain proteins interact to regulate Dictyostelium gene expression during growth and early development. Journal of Biological Chemistry, 285(30), 22927-22935. https://doi.org/10.1074/jbc.M110.139733