The WW domain protein Kibra acts upstream of Hippo in Drosophila

Roland Baumgartner; Ingrid Poernbacher; Nathalie Buser; Ernst Hafen; Hugo Stocker; Roland Franz Baumgartner

doi:10.1016/j.devcel.2009.12.013

The WW domain protein Kibra acts upstream of Hippo in Drosophila

Roland Baumgartner, Ingrid Poernbacher, Nathalie Buser, Ernst Hafen, Hugo Stocker, Roland Franz Baumgartner

214 Citationer (Scopus)

Abstract

The conserved Hippo kinase pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Whereas the function of the core kinase cascade, consisting of the serine/threonine kinases Hippo and Warts, in phosphorylating and thereby inactivating the transcriptional coactivator Yorkie is well established, much less is known about the upstream events that regulate Hippo signaling activity. The FERM domain proteins Expanded and Merlin appear to represent two different signaling branches that feed into the Hippo pathway. Signaling by the atypical cadherin Fat may act via Expanded, but how Merlin is regulated has remained elusive. Here, we show that the WW domain protein Kibra is a Hippo signaling component upstream of Hippo and Merlin. Kibra acts synergistically with Expanded, and it physically interacts with Merlin. Thus, Kibra predominantly acts in the Merlin branch upstream of the core kinase cascade to regulate Hippo signaling.

Originalsprog	Engelsk
Tidsskrift	Developmental Cell
Vol/bind	18
Udgave nummer	2
Sider (fra-til)	309-16
Antal sider	8
ISSN	1534-5807
DOI	https://doi.org/10.1016/j.devcel.2009.12.013
Status	Udgivet - 16 feb. 2010

Adgang til dokumentet

10.1016/j.devcel.2009.12.013

Citationsformater

@article{56b98370c3c94cab9eb809496cd763bb,

title = "The WW domain protein Kibra acts upstream of Hippo in Drosophila",

abstract = "The conserved Hippo kinase pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Whereas the function of the core kinase cascade, consisting of the serine/threonine kinases Hippo and Warts, in phosphorylating and thereby inactivating the transcriptional coactivator Yorkie is well established, much less is known about the upstream events that regulate Hippo signaling activity. The FERM domain proteins Expanded and Merlin appear to represent two different signaling branches that feed into the Hippo pathway. Signaling by the atypical cadherin Fat may act via Expanded, but how Merlin is regulated has remained elusive. Here, we show that the WW domain protein Kibra is a Hippo signaling component upstream of Hippo and Merlin. Kibra acts synergistically with Expanded, and it physically interacts with Merlin. Thus, Kibra predominantly acts in the Merlin branch upstream of the core kinase cascade to regulate Hippo signaling.",

keywords = "Animals, Animals, Genetically Modified, Apoptosis, Cell Count, Cell Line, Drosophila, Drosophila Proteins, Epistasis, Genetic, Gene Expression Regulation, Developmental, Genes, Insect, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mutation, Neurofibromin 2, Nuclear Proteins, Organ Size, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Signal Transduction, Trans-Activators, Tumor Suppressor Proteins",

author = "Roland Baumgartner and Ingrid Poernbacher and Nathalie Buser and Ernst Hafen and Hugo Stocker and Baumgartner, {Roland Franz}",

year = "2010",

month = feb,

day = "16",

doi = "10.1016/j.devcel.2009.12.013",

language = "English",

volume = "18",

pages = "309--16",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - The WW domain protein Kibra acts upstream of Hippo in Drosophila

AU - Baumgartner, Roland

AU - Poernbacher, Ingrid

AU - Buser, Nathalie

AU - Hafen, Ernst

AU - Stocker, Hugo

AU - Baumgartner, Roland Franz

PY - 2010/2/16

Y1 - 2010/2/16

N2 - The conserved Hippo kinase pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Whereas the function of the core kinase cascade, consisting of the serine/threonine kinases Hippo and Warts, in phosphorylating and thereby inactivating the transcriptional coactivator Yorkie is well established, much less is known about the upstream events that regulate Hippo signaling activity. The FERM domain proteins Expanded and Merlin appear to represent two different signaling branches that feed into the Hippo pathway. Signaling by the atypical cadherin Fat may act via Expanded, but how Merlin is regulated has remained elusive. Here, we show that the WW domain protein Kibra is a Hippo signaling component upstream of Hippo and Merlin. Kibra acts synergistically with Expanded, and it physically interacts with Merlin. Thus, Kibra predominantly acts in the Merlin branch upstream of the core kinase cascade to regulate Hippo signaling.

AB - The conserved Hippo kinase pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Whereas the function of the core kinase cascade, consisting of the serine/threonine kinases Hippo and Warts, in phosphorylating and thereby inactivating the transcriptional coactivator Yorkie is well established, much less is known about the upstream events that regulate Hippo signaling activity. The FERM domain proteins Expanded and Merlin appear to represent two different signaling branches that feed into the Hippo pathway. Signaling by the atypical cadherin Fat may act via Expanded, but how Merlin is regulated has remained elusive. Here, we show that the WW domain protein Kibra is a Hippo signaling component upstream of Hippo and Merlin. Kibra acts synergistically with Expanded, and it physically interacts with Merlin. Thus, Kibra predominantly acts in the Merlin branch upstream of the core kinase cascade to regulate Hippo signaling.

KW - Animals

KW - Animals, Genetically Modified

KW - Apoptosis

KW - Cell Count

KW - Cell Line

KW - Drosophila

KW - Drosophila Proteins

KW - Epistasis, Genetic

KW - Gene Expression Regulation, Developmental

KW - Genes, Insect

KW - Intracellular Signaling Peptides and Proteins

KW - Membrane Proteins

KW - Mutation

KW - Neurofibromin 2

KW - Nuclear Proteins

KW - Organ Size

KW - Protein Structure, Tertiary

KW - Protein-Serine-Threonine Kinases

KW - Signal Transduction

KW - Trans-Activators

KW - Tumor Suppressor Proteins

U2 - 10.1016/j.devcel.2009.12.013

DO - 10.1016/j.devcel.2009.12.013

M3 - Journal article

C2 - 20159600

SN - 1534-5807

VL - 18

SP - 309

EP - 316

JO - Developmental Cell

JF - Developmental Cell

IS - 2

ER -

The WW domain protein Kibra acts upstream of Hippo in Drosophila

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater