The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway.
Activation of the Raf kinase by GTP-bound Ras is a poorly understood step in receptor tyrosine kinase signaling pathways. One such pathway, the epidermal growth factor receptor (EGFR) pathway, is critical for cell differentiation, survival, and cell cycle regulation in many systems, including the Drosophila eye. We have identified a mutation in a novel gene, aveugle, based on its requirement for normal photoreceptor differentiation. The phenotypes of aveugle mutant cells in the eye and wing imaginal discs resemble those caused by reduction of EGFR pathway function. We show that aveugle is required between ras and raf for EGFR signaling in the eye and for mitogen-activated protein kinase phosphorylation in cell culture. aveugle encodes a small protein with a sterile alpha motif (SAM) domain that can physically interact with the scaffold protein connector enhancer of Ksr (Cnk). We propose that Aveugle acts together with Cnk to promote Raf activation, perhaps by recruiting an activating kinase.
Roignant
Jean-Yves
JY
Skirball Institute for Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Hamel
Sophie
S
Janody
Florence
F
Treisman
Jessica E
JE
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008297:Male; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C115753:CNK protein, Drosophila; D029721:Drosophila Proteins; D004247:DNA; D066246:ErbB Receptors; D048490:raf Kinases