Hedgehog-regulated atypical PKC promotes phosphorylation and activation of Smoothened and Cubitus interruptus in Drosophila

Kai Jiang, Yajuan Liu, Junkai Fan, Garretson Epperly, Tianyan Gao, Jin Jiang, Jianhang Jia

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Smoothened (Smo) is essential for transduction of the Hedgehog (Hh) signal in both insects and vertebrates. Cell surface/cilium accumulation of Smo is thought to play an important role in Hh signaling, but how the localization of Smo is controlled remains poorly understood. In this study, we demonstrate that atypical PKC (aPKC) regulates Smo phosphorylation and basolateral accumulation in Drosophila wings. Inactivation of aPKC by either RNAi or a mutation inhibits Smo basolateral accumulation and attenuates Hh target gene expression. In contrast, expression of constitutively active aPKC elevates basolateral accumulation of Smo and promotes Hh signaling. The aPKC-mediated phosphorylation of Smo at Ser680 promotes Ser683 phosphorylation by casein kinase 1(CK1), and these phosphorylation events elevate Smo activity in vivo. Moreover, aPKC has an additional positive role in Hh signaling by regulating the activity of Cubitus interruptus (Ci) through phosphorylation of the Zn finger DNA-binding domain. Finally, the expression of aPKC is up-regulated by Hh signaling in a Ci-dependent manner. Our findings indicate a direct involvement of aPKC in Hh signaling beyond its role in cell polarity.

Original languageEnglish (US)
Pages (from-to)E4842-E4850
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number45
DOIs
StatePublished - Nov 11 2014

Fingerprint

Hedgehogs
Drosophila
Phosphorylation
Casein Kinase I
Cell Polarity
Cilia
RNA Interference
Insects
Vertebrates
Signal Transduction
Gene Expression
Mutation
DNA

Keywords

  • aPKC
  • Ci
  • Hh
  • Par6
  • Smo

ASJC Scopus subject areas

  • General

Cite this

Hedgehog-regulated atypical PKC promotes phosphorylation and activation of Smoothened and Cubitus interruptus in Drosophila. / Jiang, Kai; Liu, Yajuan; Fan, Junkai; Epperly, Garretson; Gao, Tianyan; Jiang, Jin; Jia, Jianhang.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 45, 11.11.2014, p. E4842-E4850.

Research output: Contribution to journalArticle

@article{deb987e70c22482dbf88bed7115b22f8,
title = "Hedgehog-regulated atypical PKC promotes phosphorylation and activation of Smoothened and Cubitus interruptus in Drosophila",
abstract = "Smoothened (Smo) is essential for transduction of the Hedgehog (Hh) signal in both insects and vertebrates. Cell surface/cilium accumulation of Smo is thought to play an important role in Hh signaling, but how the localization of Smo is controlled remains poorly understood. In this study, we demonstrate that atypical PKC (aPKC) regulates Smo phosphorylation and basolateral accumulation in Drosophila wings. Inactivation of aPKC by either RNAi or a mutation inhibits Smo basolateral accumulation and attenuates Hh target gene expression. In contrast, expression of constitutively active aPKC elevates basolateral accumulation of Smo and promotes Hh signaling. The aPKC-mediated phosphorylation of Smo at Ser680 promotes Ser683 phosphorylation by casein kinase 1(CK1), and these phosphorylation events elevate Smo activity in vivo. Moreover, aPKC has an additional positive role in Hh signaling by regulating the activity of Cubitus interruptus (Ci) through phosphorylation of the Zn finger DNA-binding domain. Finally, the expression of aPKC is up-regulated by Hh signaling in a Ci-dependent manner. Our findings indicate a direct involvement of aPKC in Hh signaling beyond its role in cell polarity.",
keywords = "aPKC, Ci, Hh, Par6, Smo",
author = "Kai Jiang and Yajuan Liu and Junkai Fan and Garretson Epperly and Tianyan Gao and Jin Jiang and Jianhang Jia",
year = "2014",
month = "11",
day = "11",
doi = "10.1073/pnas.1417147111",
language = "English (US)",
volume = "111",
pages = "E4842--E4850",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "45",

}

TY - JOUR

T1 - Hedgehog-regulated atypical PKC promotes phosphorylation and activation of Smoothened and Cubitus interruptus in Drosophila

AU - Jiang, Kai

AU - Liu, Yajuan

AU - Fan, Junkai

AU - Epperly, Garretson

AU - Gao, Tianyan

AU - Jiang, Jin

AU - Jia, Jianhang

PY - 2014/11/11

Y1 - 2014/11/11

N2 - Smoothened (Smo) is essential for transduction of the Hedgehog (Hh) signal in both insects and vertebrates. Cell surface/cilium accumulation of Smo is thought to play an important role in Hh signaling, but how the localization of Smo is controlled remains poorly understood. In this study, we demonstrate that atypical PKC (aPKC) regulates Smo phosphorylation and basolateral accumulation in Drosophila wings. Inactivation of aPKC by either RNAi or a mutation inhibits Smo basolateral accumulation and attenuates Hh target gene expression. In contrast, expression of constitutively active aPKC elevates basolateral accumulation of Smo and promotes Hh signaling. The aPKC-mediated phosphorylation of Smo at Ser680 promotes Ser683 phosphorylation by casein kinase 1(CK1), and these phosphorylation events elevate Smo activity in vivo. Moreover, aPKC has an additional positive role in Hh signaling by regulating the activity of Cubitus interruptus (Ci) through phosphorylation of the Zn finger DNA-binding domain. Finally, the expression of aPKC is up-regulated by Hh signaling in a Ci-dependent manner. Our findings indicate a direct involvement of aPKC in Hh signaling beyond its role in cell polarity.

AB - Smoothened (Smo) is essential for transduction of the Hedgehog (Hh) signal in both insects and vertebrates. Cell surface/cilium accumulation of Smo is thought to play an important role in Hh signaling, but how the localization of Smo is controlled remains poorly understood. In this study, we demonstrate that atypical PKC (aPKC) regulates Smo phosphorylation and basolateral accumulation in Drosophila wings. Inactivation of aPKC by either RNAi or a mutation inhibits Smo basolateral accumulation and attenuates Hh target gene expression. In contrast, expression of constitutively active aPKC elevates basolateral accumulation of Smo and promotes Hh signaling. The aPKC-mediated phosphorylation of Smo at Ser680 promotes Ser683 phosphorylation by casein kinase 1(CK1), and these phosphorylation events elevate Smo activity in vivo. Moreover, aPKC has an additional positive role in Hh signaling by regulating the activity of Cubitus interruptus (Ci) through phosphorylation of the Zn finger DNA-binding domain. Finally, the expression of aPKC is up-regulated by Hh signaling in a Ci-dependent manner. Our findings indicate a direct involvement of aPKC in Hh signaling beyond its role in cell polarity.

KW - aPKC

KW - Ci

KW - Hh

KW - Par6

KW - Smo

UR - http://www.scopus.com/inward/record.url?scp=84909606348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84909606348&partnerID=8YFLogxK

U2 - 10.1073/pnas.1417147111

DO - 10.1073/pnas.1417147111

M3 - Article

C2 - 25349414

AN - SCOPUS:84909606348

VL - 111

SP - E4842-E4850

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 45

ER -