Hedgehog signal transduction: recent findings

被引:136
作者
Nybakken, K
Perrimon, N
机构
[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0959-437X(02)00333-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The Hedgehog (Hh) family of signaling molecules are key agents in patterning numerous types of tissues. Mutations in Hh and its downstream signaling molecules are also associated with numerous oncogenic and disease states. Consequently, understanding the mechanisms by which Hh signals are transduced is important for understanding both development and disease. Recent studies have clarified several aspects of Hh signal transduction. Several new Sonic Hedgehog binding partners have been identified. Cholesterol and palmitic acid modifications of Hh and Sonic hedgehog have been examined in greater detail. Characterization of the trafficking patterns of the Patched and Smoothened proteins has demonstrated that these two proteins function very differently from the previously established models. The Fused kinase has been demonstrated to phosphorylate the kinesin-like protein Costal2 and the sites identified, while Cubitus interruptus has been shown to be phosphorylated in a hierarchical manner by three different kinases. Finally, the interactions, both genetic and physical, between Fused, Costal2, Cubitus interruptus, and Suppressor of Fused have been further elucidated.
引用
收藏
页码:503 / 511
页数:9
相关论文
共 57 条
[11]   Nuclear trafficking of cubitus interruptus in the transcriptional regulation of hedgehog target gene expression [J].
Chen, CH ;
von Kessler, DP ;
Park, WJ ;
Beachy, PA .
CELL, 1999, 98 (03) :305-316
[12]   Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex [J].
Cheng, SY ;
Bishop, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (08) :5442-5447
[13]   Megalin and cubilin: Multifunctional endocytic receptors [J].
Christensen, EI ;
Birn, H .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (04) :258-268A
[14]   Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein [J].
Chuang, PT ;
McMahon, AP .
NATURE, 1999, 397 (6720) :617-621
[15]   STRUCTURE, FUNCTION, AND CHROMOSOME MAPPING OF THE GROWTH-SUPPRESSING HUMAN HOMOLOG OF THE MURINE GAS1 GENE [J].
DELSAL, G ;
COLLAVIN, L ;
RUARO, ME ;
EDOMI, P ;
SACCONE, S ;
DELLAVALLE, G ;
SCHNEIDER, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (05) :1848-1852
[16]   THE GROWTH ARREST-SPECIFIC GENE, GAS1, IS INVOLVED IN GROWTH SUPPRESSION [J].
DELSAL, G ;
RUARO, ME ;
PHILIPSON, L ;
SCHNEIDER, C .
CELL, 1992, 70 (04) :595-607
[17]  
DELSAL G, 1995, MOL CELL BIOL, V15, P7152
[18]   Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened [J].
Denef, N ;
Neubüser, D ;
Perez, L ;
Cohen, SM .
CELL, 2000, 102 (04) :521-531
[19]   Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway [J].
Eggenschwiler, JT ;
Espinoza, E ;
Anderson, KV .
NATURE, 2001, 412 (6843) :194-198
[20]   The fused protein kinase regulates Hedgehog-stimulated transcriptional activation in Drosophila Schneider 2 cells [J].
Fukumoto, T ;
Watanabe-Fukunaga, R ;
Fujisawa, K ;
Nagata, S ;
Fukunaga, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) :38441-38448