GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16844358

From GONUTS
Jump to: navigation, search
Citation

Pai, LM, Wang, PY, Chen, SR, Barcelo, G, Chang, WL, Nilson, L and Schüpbach, T (2006) Differential effects of Cbl isoforms on Egfr signaling in Drosophila. Mech. Dev. 123:450-62

Abstract

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.

Links

PubMed Online version:10.1016/j.mod.2006.04.001

Keywords

Alternative Splicing; Animals; Body Patterning; Drosophila Proteins/chemistry; Drosophila Proteins/physiology; Drosophila melanogaster; Endocytosis; Female; Gene Expression Regulation, Developmental; In Situ Hybridization; Ovary/metabolism; Phenotype; Protein Isoforms; Protein Structure, Tertiary; Proto-Oncogene Proteins c-cbl/chemistry; Proto-Oncogene Proteins c-cbl/physiology; Receptor, Epidermal Growth Factor/metabolism; Receptor, Epidermal Growth Factor/physiology; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q9VSK2

located_in

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9VSK2

involved_in

GO:0048260: positive regulation of receptor-mediated endocytosis

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0003392

P

Seeded From UniProt

complete

DROME:Q9VSK2

involved_in

GO:0042059: negative regulation of epidermal growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:O46034

involved_in

GO:0042059: negative regulation of epidermal growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:O46034

part_of

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.