A Dictyostelium homologue of the metazoan Cbl proteins regulates STAT signalling

Judith Langenick, Tsuyoshi Araki, Yoko Yamada, Jeffrey G. Williams

    Research output: Contribution to journalArticle

    22 Citations (Scopus)

    Abstract

    Cbl proteins downregulate metazoan signalling pathways by ubiquitylating receptor tyrosine kinases, thereby targeting them for degradation. They contain a phosphotyrosine-binding region, comprising an EF-hand and an SH2 domain, linked to an E3 ubiquitin-ligase domain. CblA, a Dictyostelium homologue of the Cbl proteins, contains all three conserved domains. In a cblA(-) strain early development occurs normally but migrating cblA(-) slugs frequently fragment and the basal disc of the culminants that are formed are absent or much reduced. These are characteristic features of mutants in signalling by DIF-1, the low-molecular-mass prestalk and stalk cell inducer. Tyrosine phosphorylation of STATc is induced by DIF-1 but in the cblA(-) strain this response is attenuated relative to parental cells. We present evidence that CblA fulfils this function, as a positive regulator of STATc tyrosine phosphorylation, by downregulating PTP3, the protein tyrosine phosphatase responsible for dephosphorylating STATc. Thus Cbl proteins have an ancient origin but, whereas metazoan Cbl proteins regulate tyrosine kinases, the Dictyostelium Cbl regulates via a tyrosine phosphatase.

    Original languageEnglish
    Pages (from-to)3524-3530
    Number of pages7
    JournalJournal of Cell Science
    Volume121
    Issue number21
    Early online date7 Oct 2008
    DOIs
    Publication statusPublished - 1 Nov 2008

    Keywords

    • Cbl
    • SH2 domain
    • Dictyostelium
    • STAT
    • DIF
    • PTP
    • Growth factor receptor
    • Protooncogene C-CBL
    • Transcription factor
    • Gene expression
    • EGF receptor
    • Tyrosine phosphorylation
    • Negative regulator
    • V-CBL
    • Discoideum
    • Kinase

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