Reference Report

Reference
Citation	Su, Y., Ospina, J.K., Zhang, J., Michelson, A.P., Schoen, A.M., Zhu, A.J. (2011). Sequential phosphorylation of smoothened transduces graded hedgehog signaling. Sci. Signal. 4(180): ra43. (Export to RIS)
FlyBase ID	FBrf0216577
Publication Type	Research paper
PubMed ID	21730325
PubMed Abstract	The correct interpretation of a gradient of the morphogen Hedgehog (Hh) during development requires phosphorylation of the Hh signaling activator Smoothened (Smo); however, the molecular mechanism by which Smo transduces graded Hh signaling is not well understood. We show that regulation of the phosphorylation status of Smo by distinct phosphatases at specific phosphorylated residues creates differential thresholds of Hh signaling. Phosphorylation of Smo was initiated by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) and further enhanced by casein kinase I (CKI). We found that protein phosphatase 1 (PP1) directly dephosphorylated PKA-phosphorylated Smo to reduce signaling mediated by intermediate concentrations of Hh, whereas PP2A specifically dephosphorylated PKA-primed, CKI-phosphorylated Smo to restrict signaling by high concentrations of Hh. We also established a functional link between sequentially phosphorylated Smo species and graded Hh activity. Thus, we propose a sequential phosphorylation model in which precise interpretation of morphogen concentration can be achieved upon versatile phosphatase-mediated regulation of the phosphorylation status of an essential activator in developmental signaling.
DOI	10.1126/scisignal.2001747
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Sci. Signal.
Title	Science signaling
Publication Year
ISBN/ISSN	1937-9145
Data from Reference
Alleles (12)
	NiPp1^{Scer\UAS.T:Ivir\HA1} Scer\GAL4^ap-md544 Scer\GAL4^Bx-MS1096 smo² smo^{CK1.Scer\UAS.T:Ivir\HA1} smo^{GSK3.Scer\UAS.T:Ivir\HA1} smo^{PKA.Scer\UAS.T:Ivir\HA1} smo^{Scer\UAS.cvdHa} wdb^dn.Scer\UAS wdb^IP wdb^Scer\UAS.cHa wdb^{Scer\UAS.T:Ivir\HA1}
Constructs (8)
	P{UAS(-FRT)smo.HA-CK1} P{UAS(-FRT)smo.HA-GSK3} P{UAS(-FRT)smo.HA-PKA} P{UAS-NiPp1.HA} P{UAS-smo.vdH} P{UAS-wdb.dn} P{UAS-wdb.H} P{UAS-wdb.HA}
Genes (19)
	CG4733 ci dpp flw kn mts NiPp1 Pp1-13C Pp1-87B Pp1α-96A Pp2A-29B PP2A-B' Pp4-19C ptc Scer\GAL4 smo T:Ivir\HA1 tws wdb
Insertions (2)
	P{GawB}ap^md544 P{GawB}Bx^MS1096
Natural transposons (1)
	P-element