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Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown

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Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown. / Sopko, Richelle; Silva, Elizabeth; Clayton, Lesley; Gardano, Laura; Barrios-Rodiles, Miriam; Wrana, Jeff; Varelas, Xaralabos; Arbouzova, Natalia I.; Shaw, Sanjeev; Saburi, Sakura; Matakatsu, Hitoshi; Blair, Seth; McNeill, Helen.

In: Current Biology, Vol. 19, No. 13, 14.07.2009, p. 1112-1117.

Research output: Contribution to journalArticle

Harvard

Sopko, R, Silva, E, Clayton, L, Gardano, L, Barrios-Rodiles, M, Wrana, J, Varelas, X, Arbouzova, NI, Shaw, S, Saburi, S, Matakatsu, H, Blair, S & McNeill, H 2009, 'Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown' Current Biology, vol 19, no. 13, pp. 1112-1117., 10.1016/j.cub.2009.05.049

APA

Sopko, R., Silva, E., Clayton, L., Gardano, L., Barrios-Rodiles, M., Wrana, J., ... McNeill, H. (2009). Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown. Current Biology, 19(13), 1112-1117. 10.1016/j.cub.2009.05.049

Vancouver

Sopko R, Silva E, Clayton L, Gardano L, Barrios-Rodiles M, Wrana J et al. Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown. Current Biology. 2009 Jul 14;19(13):1112-1117. Available from: 10.1016/j.cub.2009.05.049

Author

Sopko, Richelle; Silva, Elizabeth; Clayton, Lesley; Gardano, Laura; Barrios-Rodiles, Miriam; Wrana, Jeff; Varelas, Xaralabos; Arbouzova, Natalia I.; Shaw, Sanjeev; Saburi, Sakura; Matakatsu, Hitoshi; Blair, Seth; McNeill, Helen / Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown.

In: Current Biology, Vol. 19, No. 13, 14.07.2009, p. 1112-1117.

Research output: Contribution to journalArticle

Bibtex - Download

@article{6a9d877b8ac04d93b33fd12245c09227,
title = "Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown",
author = "Richelle Sopko and Elizabeth Silva and Lesley Clayton and Laura Gardano and Miriam Barrios-Rodiles and Jeff Wrana and Xaralabos Varelas and Arbouzova, {Natalia I.} and Sanjeev Shaw and Sakura Saburi and Hitoshi Matakatsu and Seth Blair and Helen McNeill",
year = "2009",
doi = "10.1016/j.cub.2009.05.049",
volume = "19",
number = "13",
pages = "1112--1117",
journal = "Current Biology",
issn = "0960-9822",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown

A1 - Sopko,Richelle

A1 - Silva,Elizabeth

A1 - Clayton,Lesley

A1 - Gardano,Laura

A1 - Barrios-Rodiles,Miriam

A1 - Wrana,Jeff

A1 - Varelas,Xaralabos

A1 - Arbouzova,Natalia I.

A1 - Shaw,Sanjeev

A1 - Saburi,Sakura

A1 - Matakatsu,Hitoshi

A1 - Blair,Seth

A1 - McNeill,Helen

AU - Sopko,Richelle

AU - Silva,Elizabeth

AU - Clayton,Lesley

AU - Gardano,Laura

AU - Barrios-Rodiles,Miriam

AU - Wrana,Jeff

AU - Varelas,Xaralabos

AU - Arbouzova,Natalia I.

AU - Shaw,Sanjeev

AU - Saburi,Sakura

AU - Matakatsu,Hitoshi

AU - Blair,Seth

AU - McNeill,Helen

PY - 2009/7/14

Y1 - 2009/7/14

N2 - <p>The Drosophila tumor suppressor gene fat encodes a large cadherin that regulates growth and a form of tissue organization known as planar cell polarity (PCP). Fat regulates growth via the Hippo kinase pathway [1-4], which controls expression of genes promoting cell proliferation and inhibiting apoptosis (reviewed in [5-11]). The Hippo pathway is highly conserved and is implicated in the regulation of mammalian growth and cancer development [12-18]. Genetic studies suggest that Fat activity is regulated by binding to another large cadherin, Dachsous (Ds) [19-25]. The tumor suppressor discs overgrown (dco)/Casein Kinase I delta/epsilon also regulates Hippo activity and PCP [1, 26,27]. The biochemical natureof how Fat, Ds, and Dco interact to regulate these pathways is poorly understood. Here we demonstrate that Fat is cleaved to generate 450 kDa and 110 kDa fragments (Fat(450) and Fat(110)). Fat(110) contains the cytoplasmic and transmembrane domain. The cytoplasmic domain of Fat binds Dco and is phosphorylated by Dco at multiple sites. Importantly, we show Fat forms cis-dimers and that Fat phosphorylation is regulated by Dachsous and Dco in vivo. We propose that Ds regulates Dco-dependent phosphorylation of Fat and Fat-associated proteins to control Fat signaling in growth and PCP.</p>

AB - <p>The Drosophila tumor suppressor gene fat encodes a large cadherin that regulates growth and a form of tissue organization known as planar cell polarity (PCP). Fat regulates growth via the Hippo kinase pathway [1-4], which controls expression of genes promoting cell proliferation and inhibiting apoptosis (reviewed in [5-11]). The Hippo pathway is highly conserved and is implicated in the regulation of mammalian growth and cancer development [12-18]. Genetic studies suggest that Fat activity is regulated by binding to another large cadherin, Dachsous (Ds) [19-25]. The tumor suppressor discs overgrown (dco)/Casein Kinase I delta/epsilon also regulates Hippo activity and PCP [1, 26,27]. The biochemical natureof how Fat, Ds, and Dco interact to regulate these pathways is poorly understood. Here we demonstrate that Fat is cleaved to generate 450 kDa and 110 kDa fragments (Fat(450) and Fat(110)). Fat(110) contains the cytoplasmic and transmembrane domain. The cytoplasmic domain of Fat binds Dco and is phosphorylated by Dco at multiple sites. Importantly, we show Fat forms cis-dimers and that Fat phosphorylation is regulated by Dachsous and Dco in vivo. We propose that Ds regulates Dco-dependent phosphorylation of Fat and Fat-associated proteins to control Fat signaling in growth and PCP.</p>

U2 - 10.1016/j.cub.2009.05.049

DO - 10.1016/j.cub.2009.05.049

M1 - Article

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 13

VL - 19

SP - 1112

EP - 1117

ER -

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