Competition between SOCS36E and Drk modulates Sevenless receptor tyrosine kinase activity.
Modulation of signalling pathways can trigger different cellular responses, including differences in cell fate. This modulation can be achieved by controlling the pathway activity with great precision to ensure robustness and reproducibility of the specification of cell fate. The development of the photoreceptor R7 in the Drosophila melanogaster retina has become a model in which to investigate the control of cell signalling. During R7 specification, a burst of Ras small GTPase (Ras) and mitogen-activated protein kinase (MAPK) controlled by Sevenless receptor tyrosine kinase (Sev) is required. Several cells in each ommatidium express sev. However, the spatiotemporal expression of the boss ligand and the action of negative regulators of the Sev pathway will restrict the R7 fate to a single cell. The Drosophila suppressor of cytokine signalling 36E (SOCS36E) protein contains an SH2 domain and acts as a Sev signalling attenuator. By contrast, downstream of receptor kinase (Drk), the fly homolog of the mammalian Grb2 adaptor protein, which also contains an SH2 domain, acts as a positive activator of the pathway. Here, we apply the Förster resonance energy transfer (FRET) assay to transfected Drosophila S2 cells and demonstrate that Sev binds directly to either the suppressor protein SOCS36E or the adaptor protein Drk. We propose a mechanistic model in which the competition between these two proteins for binding to the same docking site results in either attenuation of the Sev transduction in cells that should not develop R7 photoreceptors or amplification of the Ras-MAPK signal only in the R7 precursor.
Almudi
Isabel
I
Departament de Genètica, Facultat de Biologia and Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain.
Corominas
Montserrat
M
Serras
Florenci
F
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005136:Eye Proteins / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014162:Transfection; D018909:src Homology Domains
D029721:Drosophila Proteins; D005136:Eye Proteins; C460659:Socs36E protein, Drosophila; D050826:Suppressor of Cytokine Signaling Proteins; C080530:drk protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila