Identification of Genomic Regions That Interact With a Viable Allele of the Drosophila Protein Tyrosine Phosphatase Corkscrew

Corresponding author: Lizabeth A. Perkins, Pediatric Surgical Research Labs, Warren 10, Massachusetts General Hospital, 32 Fruit St., Boston, MA 02114., perkins{at}helix.mgh.harvard.edu (E-mail)

Communicating editor: T. SCHÜPBACH

Signaling by receptor tyrosine kinases (RTKs) is critical for a multitude of developmental decisions and processes. Among the molecules known to transduce the RTK-generated signal is the nonreceptor protein tyrosine phosphatase Corkscrew (Csw). Previously, Csw has been demonstrated to function throughout the Drosophila life cycle and, among the RTKs tested, Csw is essential in the Torso, Sevenless, EGF, and Breathless/FGF RTK pathways. While the biochemical function of Csw remains to be unambiguously elucidated, current evidence suggests that Csw plays more than one role during transduction of the RTK signal and, further, the molecular mechanism of Csw function differs depending upon the RTK in question. The isolation and characterization of a new, spontaneously arising, viable allele of csw, csw^lf, has allowed us to undertake a genetic approach to identify loci required for Csw function. The rough eye and wing vein gap phenotypes exhibited by adult flies homo- or hemizygous for csw^lf has provided a sensitized background from which we have screened a collection of second and third chromosome deficiencies to identify 33 intervals that enhance and 21 intervals that suppress these phenotypes. We have identified intervals encoding known positive mediators of RTK signaling, e.g., drk, dos, Egfr, E(Egfr)B56, pnt, Ras1, rolled/MAPK, sina, spen, Src64B, Star, Su(Raf)3C, and vein, as well as known negative mediators of RTK signaling, e.g., aos, ed, net, Src42A, sty, and su(ve). Of particular interest are the 5 lethal enhancing intervals and 14 suppressing intervals for which no candidate genes have been identified.

This article has been cited by other articles:

				G. D. Raffel, T. Mercher, H. Shigematsu, I. R. Williams, D. E. Cullen, K. Akashi, O. A. Bernard, and D. G. Gilliland Ott1(Rbm15) has pleiotropic roles in hematopoietic development PNAS, April 3, 2007; 104(14): 6001 - 6006. [Abstract] [Full Text] [PDF]

				B. D. Gelb and M. Tartaglia Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R220 - R226. [Abstract] [Full Text] [PDF]

				L. A. Jarvis, S. J. Toering, M. A. Simon, M. A. Krasnow, and R. K. Smith-Bolton Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases Development, March 15, 2006; 133(6): 1133 - 1142. [Abstract] [Full Text] [PDF]

				K. Oishi, K. Gaengel, S. Krishnamoorthy, K. Kamiya, I.-K. Kim, H. Ying, U. Weber, L. A. Perkins, M. Tartaglia, M. Mlodzik, et al. Transgenic Drosophila models of Noonan syndrome causing PTPN11 gain-of-function mutations Hum. Mol. Genet., February 15, 2006; 15(4): 543 - 553. [Abstract] [Full Text] [PDF]

				J. A. McDonald, E. M. Pinheiro, and D. J. Montell PVF1, a PDGF/VEGF homolog, is sufficient to guide border cells and interacts genetically with Taiman Development, August 1, 2003; 130(15): 3469 - 3478. [Abstract] [Full Text] [PDF]