Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye.
Receptor tyrosine kinases such as the EGF receptor transduce extracellular signals into multiple cellular responses. In the developing Drosophila eye, EGFR activity triggers cell differentiation. Here we focus on three additional cell autonomous aspects of EGFR function and their coordination with differentiation, namely, withdrawal from the cell cycle, mitosis, and cell survival. We find that, whereas differentiation requires intense signaling, dependent on multiple reinforcing ligands, lesser EGFR activity maintains cell cycle arrest, promotes mitosis, and protects against cell death. Each response requires the same Ras, Raf, MAPK, and Pnt signal transduction pathway. Mitotic and survival responses also involve Pnt-independent branches, perhaps explaining how survival and mitosis can occur independently. Our results suggest that, rather than triggering all or none responses, EGFR coordinates partially independent processes as the eye differentiates.
Yang
Lihui
L
Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Baker
Nicholas E
NE
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics; D002470:Cell Survival / Q000502:physiology*; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors; D015854:Up-Regulation / Q000235:genetics; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006133:Growth Substances; C465500:Krn protein, Drosophila; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C083884:pnt protein, Drosophila; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins