文档介绍：Copyright 2000 by the ics Society of America
A ic Screen for Modifiers of a Kinase Suppressor of Ras-Dependent
Rough Eye Phenotype in Drosophila
Marc Therrien,*,1 Deborah K. Morrison,† Allan M. Wong* and Gerald M. Rubin*
*Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200
and †Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research
and Development Center, Frederick, Maryland 21702
Manuscript received May 3, 2000
Accepted for publication July 25, 2000
ABSTRACT
kinase suppressor of Ras (ksr) encodes a putative protein kinase that by ic criteria appears to function
downstream of RAS in multiple receptor tyrosine kinase (RTK) pathways. While biochemical evidence
suggests that the role of KSR is closely linked to the signal transduction mechanism of the MAPK cascade,
the precise molecular function of KSR remains unresolved. To further elucidate the role of KSR and to
identify proteins that may be required for KSR function, we conducted a dominant modifier screen in
Drosophila based on a KSR-dependent phenotype. Overexpression of the KSR kinase domain in a subset
of cells during Drosophila eye development blocks photoreceptor cell differentiation and results in the
external roughening of the adult eye. Therefore, mutations in genes functioning with KSR might modify
mutagenized progeny for dominant modifiers of 185,000ف the KSR-dependent phenotype. We screened
the KSR-dependent rough eye phenotype. A total of plementation groups of Enhancers and four
complementation groups of Suppressors were derived. Ten of plementation groups correspond
to mutations in ponents of the Ras1 pathway, demonstrating the ability of the screen to
specifically identify loci critical for Ras1 signaling and further confirming a role for KSR in Ras1 signaling.
In addition, we have identified 4 plementatio