MASK, a large ankyrin repeat and KH domain-containing protein involved in Drosophila receptor tyrosine kinase signaling.
The receptor tyrosine kinases Sevenless (SEV) and the Epidermal growth factor receptor (EGFR) are required for the proper development of the Drosophila eye. The protein tyrosine phosphatase Corkscrew (CSW) is a common component of many RTK signaling pathways, and is required for signaling downstream of SEV and EGFR. In order to identify additional components of these signaling pathways, mutations that enhanced the phenotype of a dominant negative form of Corkscrew were isolated. This genetic screen identified the novel signaling molecule MASK, a large protein that contains two blocks of ankyrin repeats as well as a KH domain. MASK genetically interacts with known components of these RTK signaling pathways. In the developing eye imaginal disc, loss of MASK function generates phenotypes similar to those generated by loss of other components of the SEV and EGFR pathways. These phenotypes include compromised photoreceptor differentiation, cell survival and proliferation. Although MASK is localized predominantly in the cellular cytoplasm, it is not absolutely required for MAPK activation or nuclear translocation. Based on our results, we propose that MASK is a novel mediator of RTK signaling, and may act either downstream of MAPK or transduce signaling through a parallel branch of the RTK pathway.
Smith
Rachel K
RK
Department of Biological Sciences, Stanford University, 385 Serra Mall, Stanford, CA 94305-5020, USA.
Carroll
Pamela M
PM
Allard
John D
JD
Simon
Michael A
MA
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000235:genetics* / Q000502:physiology; D004330:Drosophila / Q000196:embryology / Q000502:physiology*; D029721:Drosophila Proteins; D066246:ErbB Receptors / Q000502:physiology*; D005123:Eye / Q000196:embryology; D005136:Eye Proteins / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D016415:Sequence Alignment; D015398:Signal Transduction
D017487:Ankyrins; D029721:Drosophila Proteins; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila; C098692:Csw protein, Drosophila; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor