Differential effects of Cbl isoforms on Egfr signaling in Drosophila

Li Mei Pai, Pei Yu Wang, Shu Ru Chen, Gail Barcelo, Wei Ling Chang, Laura Nilson, Trudi Schüpbach

研究成果: 雜誌貢獻文章同行評審

21 引文 斯高帕斯(Scopus)

摘要

The Cbl family of proteins downregulate epidermal growth factor receptor (Egfr) signaling via receptor internalization and destruction. These proteins contain two functional domains, a RING finger domain with E3 ligase activity, and a proline rich domain mediating the formation of protein complexes. The Drosophila cbl gene encodes two isoforms, D-CblS and D-CblL. While both contain a RING finger domain, the proline rich domain is absent from D-CblS. We demonstrate that expression of either isoform is sufficient to rescue both the lethality of a D-cbl null mutant and the adult phenotypes characteristic of Egfr hyperactivation, suggesting that both isoforms downregulate Egfr signaling. Interestingly, targeted overexpression of D-CblL, but not D-CblS, results in phenotypes characteristic of reduced Egfr signaling and suppresses the effect of constitutive Egfr activation. The level of D-CblL was significantly correlated with the phenotypic severity of reduced Egfr signaling, suggesting that D-CblL controls the efficiency of downregulation of Egfr signaling. Furthermore, reduced dynamin function suppresses the effects of D-CblL overexpression in follicle cells, suggesting that D-CblL promotes internalization of activated receptors. D-CblL is detected in a punctate cytoplasmic pattern, whereas D-CblS is mainly localized at the follicle cell cortex. Therefore, D-CblS and D-CblL may downregulate Egfr through distinct mechanisms.
原文英語
頁(從 - 到)450-462
頁數13
期刊Mechanisms of Development
123
發行號6
DOIs
出版狀態已發佈 - 6月 2006

ASJC Scopus subject areas

  • 胚胎學
  • 發展生物學

指紋

深入研究「Differential effects of Cbl isoforms on Egfr signaling in Drosophila」主題。共同形成了獨特的指紋。

引用此