title: The Lnk/SH2B adaptor provides a fail-safe mechanism to establish the Insulin receptor-Chico interaction.
abstract: BACKGROUND
  Insulin/insulin-like growth factor signalling (IIS) has been described as one of the major pathways involved in growth control and homeostasis in multicellular organisms. Whereas its core components are well established, less is known about the molecular functions of IIS regulators. The adaptor molecule Lnk/SH2B has been implicated in IIS but the mechanism by which it promotes IIS activity has remained enigmatic.
  
  
  RESULTS
  In this study, we analyse genetic and physical interactions among InR, Chico and Lnk in Drosophila tissues. FRET analysis reveals in vivo binding between all three molecules. Genetically, Lnk acts upstream of Chico. We demonstrate that Chico's plasma membrane localisation is ensured by both its PH domain and by the interaction with Lnk. Furthermore, Lnk is able to recruit an intracellular InR fragment to the membrane.
  
  
  CONCLUSIONS
  Thus, by acting as a scaffolding molecule that ensures InR and Chico enrichment at the membrane, Lnk provides a fail-safe mechanism for IIS activation.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zürich, Wolfgang-Pauli-Strasse 16, Zürich 8093, Switzerland. stocker@imsb.biol.ethz.ch.
authors.forename: Isabel
authors.initials: I
authors.lastname: Almudi
authors.forename: Ingrid
authors.initials: I
authors.lastname: Poernbacher
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker