PTCH is internalized

Stable Identifier
R-HSA-5632677
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

After SMURF-dependent ubiquitination, PTCH1 is internalized to endocytic vesicles for degradation (Rohatgi et al, 2007; Huang et al, 2013; Yue et al, 2014). PTCH1 and SMO show reciprocal changes in localization upon Hh pathway activation, with PTCH moving from the primary cilium to internal vesicles while SMO becomes enriched in the primary cilium after ligand binding (Denef et al, 2000; Rohatgi et al, 2007; Corbit et al, 2005; Kovacs et al, 2008; reviewed in Goetz and Anderson). In mice, internalization of PTCH1 appears to be independent of SMO, while in flies, activated SMO is required to promote the SMURF-dependent downregulation of PTCH (Yue et al, 2014; Huang et al, 2013).

Literature References
PubMed ID Title Journal Year
24925320 Requirement of Smurf-mediated endocytosis of Patched1 in Sonic Hedgehog signal reception

Yue, S, Tang, LY, Tang, Y, Tang, Y, Shen, QH, Ding, J, Chen, Y, Zhang, Z, Yu, TT, Zhang, YE, Cheng, SY

Elife 2014
16136078 Vertebrate Smoothened functions at the primary cilium

Corbit, KC, Aanstad, P, Singla, V, Norman, AR, Stainier, DY, Reiter, JF

Nature 2005
18497258 Beta-arrestin-mediated localization of smoothened to the primary cilium

Kovacs, JJ, Whalen, EJ, Liu, R, Xiao, K, Kim, J, Chen, M, Wang, J, Chen, W, Lefkowitz, RJ

Science 2008
24302888 Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover

Huang, S, Zhang, Z, Zhang, C, Lv, X, Zheng, X, Chen, Z, Sun, L, Wang, H, Zhu, Y, Zhang, J, Yang, S, Lu, Y, Sun, Q, Tao, Y, Liu, F, Zhao, Y, Chen, D

PLoS Biol. 2013
10966113 Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened

Denef, N, Neubüser, D, Perez, L, Cohen, SM

Cell 2000
17641202 Patched1 regulates hedgehog signaling at the primary cilium

Rohatgi, R, Milenkovic, L, Scott, MP

Science 2007
Participants
Participant Of
Orthologous Events
Authored
Reviewed