Biochemical mechanisms of vertebrate hedgehog signaling

被引:183
作者
Kong, Jennifer H. [1 ,2 ]
Siebold, Christian [3 ]
Rohatgi, Rajat [1 ,2 ]
机构
[1] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA
[3] Univ Oxford, Div Struct Biol, Wellcome Ctr Human Genet, Oxford OX3 7BN, England
来源
DEVELOPMENT | 2019年 / 146卷 / 10期
基金
欧洲研究理事会; 美国国家卫生研究院;
关键词
Cholesterol; Hedgehog signaling; Morphogen; Patched; Primary cilium; Smoothened; PROTEIN-KINASE-A; COUPLED RECEPTOR GPR161; CHOLESTEROL-MODIFIED HEDGEHOG; STEROL-SENSING DOMAIN; MOUSE PATCHED GENE; SONIC-HEDGEHOG; LONG-RANGE; TUMOR-SUPPRESSOR; MULTISITE PHOSPHORYLATION; INTRAFLAGELLAR TRANSPORT;
D O I
10.1242/dev.166892
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Signaling pathways that mediate cell-cell communication are essential for collective cell behaviors in multicellular systems. The hedgehog (HH) pathway, first discovered and elucidated in Drosophila, is one of these iconic signaling systems that plays many roles during embryogenesis and in adults; abnormal HH signaling can lead to birth defects and cancer. We review recent structural and biochemical studies that have advanced our understanding of the vertebrate HH pathway, focusing on the mechanisms by which the HH signal is received by patched on target cells, transduced across the cell membrane by smoothened, and transmitted to the nucleus by GLI proteins to influence gene-expression programs.
引用
收藏
页数:17
相关论文
共 185 条
  • [81] Structural Basis of Wnt Recognition by Frizzled
    Janda, Claudia Y.
    Waghray, Deepa
    Levin, Aron M.
    Thomas, Christoph
    Garcia, K. Christopher
    [J]. SCIENCE, 2012, 337 (6090) : 59 - 64
  • [82] All Mammalian Hedgehog Proteins Interact with Cell Adhesion Molecule, Down-regulated by Oncogenes (CDO) and Brother of CDO (BOC) in a Conserved Manner
    Kavran, Jennifer M.
    Ward, Matthew D.
    Oladosu, Oyindamola O.
    Mulepati, Sabin
    Leahy, Daniel J.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (32) : 24584 - 24590
  • [83] Mouse dispatched mutants fall to distribute hedgehog proteins and are defective in hedgehog signaling
    Kawakami, T
    Kawcak, T
    Li, YJ
    Zhang, WH
    Hu, YM
    Chuang, PT
    [J]. DEVELOPMENT, 2002, 129 (24): : 5753 - 5765
  • [84] Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus
    Kim, Jynho
    Kato, Masaki
    Beachy, Philip A.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (51) : 21666 - 21671
  • [85] A FUNCTIONALLY CONSERVED HOMOLOGY OF THE DROSOPHILA SEGMENT POLARITY GENE-HH IS EXPRESSED IN TISSUES WITH POLARIZING ACTIVITY IN ZEBRAFISH EMBRYOS
    KRAUSS, S
    CONCORDET, JP
    INGHAM, PW
    [J]. CELL, 1993, 75 (07) : 1431 - 1444
  • [86] Crystal structures of the Burkholderia multivorans hopanoid transporter HpnN
    Kumar, Nitin
    Su, Chih-Chia
    Chou, Tsung-Han
    Radhakrishnan, Abhijith
    Delmar, Jared A.
    Rajashankar, Kanagalaghatta R.
    Yu, Edward W.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (25) : 6557 - 6562
  • [87] AUTOPROTEOLYSIS IN HEDGEHOG PROTEIN BIOGENESIS
    LEE, JJ
    EKKER, SC
    VONKESSLER, DP
    PORTER, JA
    SUN, BI
    BEACHY, PA
    [J]. SCIENCE, 1994, 266 (5190) : 1528 - 1537
  • [88] Hedgehog signalling
    Lee, Raymond Teck Ho
    Zhao, Zhonghua
    Ingham, Philip W.
    [J]. DEVELOPMENT, 2016, 143 (03): : 367 - 372
  • [89] Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1
    Lewis, PM
    Dunn, MP
    McMahon, JA
    Logan, M
    Martin, JF
    St-Jacques, B
    McMahon, AP
    [J]. CELL, 2001, 105 (05) : 599 - 612
  • [90] Morphogen gradient reconstitution reveals Hedgehog pathway design principles
    Li, Pulin
    Markson, Joseph S.
    Wang, Sheng
    Chen, Siheng
    Vachharajani, Vipul
    Elowitz, Michael B.
    [J]. SCIENCE, 2018, 360 (6388) : 543 - +