The Interactive Fly

Zygotically transcribed genes

RAS Pathway, EGF receptor-ligand complex

Ligands Argos Boss Gurken Keren Spitz trunk vein Ras pathway signaling proteins Calcineurin (regulates EGF signaling) Cbl corkscrew (a protein tyrosine phosphatase) daughter of sevenless an adaptor protein Disabled Downstream of Ras1 (Dsor1) - also known as Mek DRK (an SH3-SH2-SH3 adaptor protein - Grb 2 homolog) (See EGF-R) ebi GTPase-activating protein 1 kinase suppressor of ras leonardo (a 14-3-3 adaptor protein) MAP Kinase (preferred name: Rolled) (a kinase) Protein phosphatase 2A (PP2A) (preferred name: microtubule star) Ras oncogene at 85D (a GTPase) pico pole hole (common alternative name: raf) rolled - also known as MAP kinase RPS6-protein kinase-II rugose - PKA anchoring protein SHC-adaptor protein small wing - a PLCgamma Son of sevenless sprouty - a ras pathway antagonist twins - also known as the B subunit of Protein phosphatase 2A

Receptors EGF-receptor (synonym: Torpedo or DER) Sevenless Torso - see terminal group Cofactors Brainiac canoe echinoid egghead kekkon-1 Rhomboid rhomboid-2 (also known as stem cell tumor) roughoid Star Spitz group (Mediolateral group) Pointed Rhomboid Sichel (maternal) Single minded Spitz Star Targets Bicoid Cbl DJun Dorsal kekkon-1 phyllopod Pointed Rhomboid vav Yan Stimulators of ras pathway Abelson Interacting Protein Amnesiac

What is the ras pathway?

The ras pathway is a signal transduction cascade. In the Drosophila eye the receptor Sevenless is borne by cells that have the potential to develop into R7 photoreceptors, the last of eight photoreceptors to differentiate in each ommatidium. Signals from the ligand Boss, a seven pass transmembrane protein that serves as the ligand for Sevenless, triggers autophosphorylation in the Sevenless receptor tyrosine kinase. Phosphorylated Sevenless binds the adaptor protein DRK which subsequently interacts with SOS, a guanine nucleotide-releasing protein, which then removes GDP from inactive RAS and substitutes GTP. The substitution of GTP for GDP activates RAS protein.

Up to this point ras pathway proteins functions not as a soup of ingredients but as an ordered complex assembled in a successive fashion to the cytoplasmic tail of the receptor Sevenless. Signal amplification is not the object, but rather assembly of a multimolecular membrane associated protein complex. Subsequent events, the activation of Draf, initiate a signal transduction cascade phosphorylating and successively activating Dmek and Rolled. This cascade does in fact serve to amplify the Sevenless signal, and results in the phosphorylation and activation of the transcription factor Pointed, which then determines R7 fate.

The ras pathway is used by four receptors, each triggered by different ligands in different tissues. The targets of Ras signaling between tissues also differ. Thus the ras pathway serves to transduce signals between receptor tyrosine kinases and the nucleus. Recent studies show that there are parallel pathways to the RAS1 to Rolled phosphorylation cascade, even in Drosophila. For a newly characterized example see Hemipterous and the dorsal closure pathway. The components of these alternative pathways are currently being investigated.

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