SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc

作者: Bernard A Callus , Bernard Mathey-Prevot

DOI: 10.1038/SJ.ONC.1205618

关键词: statDrosophilidaeGeneGeneticsDrosophila melanogasterBiologyPhenotypeCell biologyJAK-STAT signaling pathwayTransgeneEye pigmentation

摘要: We have cloned a novel SOCS gene from Drosophila, socs36E, which is most homologous to the mammalian socs-5 gene. Socs36E expressed zygotically, predominantly during embryogenesis, in highly dynamic pattern. In vivo expression of SOCS36E transgenic flies results several adult phenotypes. Engrailed-GAL4 directed causes loss wing anterior cross vein, humeral outgrowths, absence halteres and eye pigmentation defects. Expression under apterous-GAL4 control resulted outstretched wings. Full penetrance these phenotypes required presence SH2 SOCS-box domains SOCS36E. The observed were consistent with defects JAK/STAT or EGF-R signalling exacerbated heterozygous for either d-jak (hopscotch), d-stat (stat92E) d-egf-r (der) genes. Conversely, inactivating one copy d-cbl gene, negative regulator d-EGF-R, partially rescued These genetic interactions imply that can suppress activities pathways disc suggest interacts multiple vivo.

参考文章(25)
A. Yoshimura, T. Ohkubo, T. Kiguchi, N.A. Jenkins, D.J. Gilbert, N.G. Copeland, T. Hara, A. Miyajima, A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. The EMBO Journal. ,vol. 14, pp. 2816- 2826 ,(1995) , 10.1002/J.1460-2075.1995.TB07281.X
Akira Matsumoto, Masaaki Masuhara, Kaoru Mitsui, Masahiro Yokouchi, Motoaki Ohtsubo, Hiroyuki Misawa, Atsushi Miyajima, Akihiko Yoshimura, CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation. Blood. ,vol. 89, pp. 3148- 3154 ,(1997) , 10.1182/BLOOD.V89.9.3148
Takaho A. Endo, Masaaki Masuhara, Masahiro Yokouchi, Ritsu Suzuki, Hiroshi Sakamoto, Kaoru Mitsui, Akira Matsumoto, Shyu Tanimura, Motoaki Ohtsubo, Hiroyuki Misawa, Tadaaki Miyazaki, Nogueira Leonor, Tadatsugu Taniguchi, Takashi Fujita, Yuzuru Kanakura, Seturo Komiya, Akihiko Yoshimura, A new protein containing an SH2 domain that inhibits JAK kinases Nature. ,vol. 387, pp. 921- 924 ,(1997) , 10.1038/43213
Nicholas A. Cacalano, David Sanden, James A. Johnston, Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras. Nature Cell Biology. ,vol. 3, pp. 460- 465 ,(2001) , 10.1038/35074525
Donald Metcalf, Christopher J. Greenhalgh, Elizabeth Viney, Tracy A. Willson, Robyn Starr, Nicos A. Nicola, Douglas J. Hilton, Warren S. Alexander, Gigantism in mice lacking suppressor of cytokine signalling-2 Nature. ,vol. 405, pp. 1069- 1073 ,(2000) , 10.1038/35016611
Robyn Starr, Tracy A. Willson, Elizabeth M. Viney, Leecia J. L. Murray, John R. Rayner, Brendan J. Jenkins, Thomas J. Gonda, Warren S. Alexander, Donald Metcalf, Nicos A. Nicola, Douglas J. Hilton, A family of cytokine-inducible inhibitors of signalling Nature. ,vol. 387, pp. 917- 921 ,(1997) , 10.1038/43206
B J Mayer, P K Jackson, R A Van Etten, D Baltimore, Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo. Molecular and Cellular Biology. ,vol. 12, pp. 609- 618 ,(1992) , 10.1128/MCB.12.2.609
T. Kamura, S. Sato, D. Haque, L. Liu, W. G. Jr. Kaelin, R. C. Conaway, J. W. Conaway, The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families Genes & Development. ,vol. 12, pp. 3872- 3881 ,(1998) , 10.1101/GAD.12.24.3872
R. Yan, H. Luo, J. E. Darnell, C. R. Dearolf, A JAK-STAT pathway regulates wing vein formation in Drosophila Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 5842- 5847 ,(1996) , 10.1073/PNAS.93.12.5842