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PMID:19680438

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Citation

Werz, C, Köhler, K, Hafen, E and Stocker, H (2009) The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS Genet. 5:e1000596

Abstract

Insulin/insulin-like growth factor signaling (IIS) plays a pivotal role in the regulation of growth at the cellular and the organismal level during animal development. Flies with impaired IIS are developmentally delayed and small due to fewer and smaller cells. In the search for new growth-promoting genes, we identified mutations in the gene encoding Lnk, the single fly member of the SH2B family of adaptor molecules. Flies lacking lnk function are viable but severely reduced in size. Furthermore, lnk mutants display phenotypes reminiscent of reduced IIS, such as developmental delay, female sterility, and accumulation of lipids. Genetic epistasis analysis places lnk downstream of the insulin receptor (InR) and upstream of phosphoinositide 3-kinase (PI3K) in the IIS cascade, at the same level as chico (encoding the single fly insulin receptor substrate [IRS] homolog). Both chico and lnk mutant larvae display a similar reduction in IIS activity as judged by the localization of a PIP(3) reporter and the phosphorylation of protein kinase B (PKB). Furthermore, chico; lnk double mutants are synthetically lethal, suggesting that Chico and Lnk fulfill independent but partially redundant functions in the activation of PI3K upon InR stimulation.

Links

PubMed PMC2716533 Online version:10.1371/journal.pgen.1000596

Keywords

Adaptor Proteins, Signal Transducing/chemistry; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Amino Acid Sequence; Animals; Body Size; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/chemistry; Drosophila melanogaster/genetics; Drosophila melanogaster/growth & development; Drosophila melanogaster/metabolism; Insulin/genetics; Insulin/metabolism; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Molecular Sequence Data; Multigene Family; Mutation; Receptor, Insulin/genetics; Receptor, Insulin/metabolism; Sequence Alignment; Signal Transduction; src Homology Domains

Significance

Annotations

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

DROME:A0A0B4LHY5

involved_in

GO:0030307: positive regulation of cell growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4LHY5

involved_in

GO:0014068: positive regulation of phosphatidylinositol 3-kinase signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4LHY5

involved_in

GO:0008286: insulin receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4LHY5

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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