ADRBK1 phosphorylates SMO dimer

Stable Identifier
R-HSA-5632672
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ciliary membrane
ReviewStatus
5/5
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ADRBK1 phosphorylates SMO dimer
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ADRBK1 phosphorylates the SMO C-terminal tail after initial phosphorylation by CSNK1A1. Phosphorylation promotes an open, activated conformation of the C-terminal tails, allowing an intramolecular interaction between tails of adjacent monomers in the SMO dimer. This Hh-dependent conformational change is required for downstream signal propagation (Chen et al, 2011; Chen et al, 2010; Zhao et al, 2007; Meloni et al, 2006; Philipp et al, 2008; reviewed in Briscoe and Therond, 2013). In Drosophila, Smo C-terminal tail phosphorylation promotes an association with the Hedgehog signaling complex (HSC) through interaction with the scaffolding kinesin-2 like protein Cos2, and ultimately results in the release of full-length Ci from the complex (Zhang et al, 2005; Ogden et al, 2003; Lum et al, 2003; reviewed in Mukhopadhyay and Rohatgi, 2014). How Hh signal is transmitted from activated SMO to downstream components in vertebrate cells is not fully established
Literature References
PubMed ID Title Journal Year
21695114 Sonic Hedgehog dependent phosphorylation by CK1? and GRK2 is required for ciliary accumulation and activation of smoothened

Chen, Y, Sasai, N, Ma, G, Yue, T, Jia, J, Briscoe, J, Jiang, J

PLoS Biol. 2011
15691767 Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus

Zhang, W, Zhao, Y, Tong, C, Wang, G, Wang, B, Jia, J, Jiang, J

Dev Cell 2005
14636583 Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2

Lum, L, Zhang, C, Oh, S, Mann, RK, von Kessler, DP, Taipale, J, Weis-Garcia, F, Gong, R, Wang, B, Beachy, PA

Mol Cell 2003
20844016 G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinase-dependent and kinase-independent mechanisms in Drosophila

Chen, Y, Li, S, Tong, C, Zhao, Y, Wang, B, Liu, Y, Jia, J, Jiang, J

Genes Dev. 2010
16630821 The ihog cell-surface proteins bind Hedgehog and mediate pathway activation

Yao, S, Lum, L, Beachy, P

Cell 2006
14614827 Identification of a functional interaction between the transmembrane protein Smoothened and the kinesin-related protein Costal2

Ogden, SK, Ascano M, Jr, Stegman, MA, Suber, LM, Hooper, JE, Robbins, DJ

Curr Biol 2003
16908539 Smoothened signal transduction is promoted by G protein-coupled receptor kinase 2

Meloni, AR, Fralish, GB, Kelly, P, Salahpour, A, Chen, JK, Wechsler-Reya, RJ, Lefkowitz, RJ, Caron, MG

Mol. Cell. Biol. 2006
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
18815277 Smoothened signaling in vertebrates is facilitated by a G protein-coupled receptor kinase

Philipp, M, Fralish, GB, Meloni, AR, Chen, W, MacInnes, AW, Barak, LS, Caron, MG

Mol. Biol. Cell 2008
23719536 The mechanisms of Hedgehog signalling and its roles in development and disease

Briscoe, J, Thérond, PP

Nat. Rev. Mol. Cell Biol. 2013
17960137 Hedgehog regulates smoothened activity by inducing a conformational switch

Zhao, Y, Tong, C, Jiang, J

Nature 2007
24845016 G-protein-coupled receptors, Hedgehog signaling and primary cilia

Mukhopadhyay, S, Rohatgi, R

Semin. Cell Dev. Biol. 2014
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein serine/threonine kinase activity of pS588, S590, T593, S595-SMO dimer:CSNK1A1:ADRBK1 [ciliary membrane]

Physical Entity
pS588, S590, T593, S595-SMO dimer:CSNK1A1:ADRBK1 [ciliary membrane] (Homo sapiens)
Activity
protein serine/threonine kinase activity (GO:0004674)
Inferred From
Adrbk1 phosphorylates Smo dimer (Mus musculus)
Authored
Rothfels, K  (2014-10-24)
Reviewed
Liu, Y C  (2014-11-09)
Created
Rothfels, K  (2014-10-28)
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