Abstract
The Hippo tumor suppressor pathway plays an important role in tissue homeostasis that ensures development of functional organs at proper size. The YAP transcription coactivator is a major effector of the Hippo pathway and is phosphorylated and inactivated by the Hippo pathway kinases Lats1/2. It has recently been shown that YAP activity is regulated by G-protein-coupled receptor signaling. Here we demonstrate that cyclic adenosine monophosphate (cAMP), a second messenger downstream from Gas-coupled receptors, acts through protein kinase A (PKA) and Rho GTPases to stimulate Lats kinases and YAP phosphorylation. We also show that inactivation of YAP is crucial for PKA-induced adipogenesis. In addition, PKA activation in Drosophila inhibits the expression of Yorki (Yki, a YAP ortholog) target genes involved in cell proliferation and death. Taken together, our study demonstrates that Hippo-YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1223-1232 |
| Number of pages | 10 |
| Journal | Genes and Development |
| Volume | 27 |
| Issue number | 11 |
| DOIs | |
| State | Published - Feb 1 2013 |
Fingerprint
Keywords
- Adipogenesis
- Hippo
- PKA
- Proliferation
- YAP
ASJC Scopus subject areas
- Genetics
- Developmental Biology
Cite this
Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. / Yu, Fa Xing; Zhang, Yifan; Park, Hyun Woo; Jewell, Jenna L.; Chen, Qian; Deng, Yaoting; Pan, Duojia; Taylor, Susan S.; Lai, Zhi Chun; Guan, Kun Liang.
In: Genes and Development, Vol. 27, No. 11, 01.02.2013, p. 1223-1232.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation
AU - Yu, Fa Xing
AU - Zhang, Yifan
AU - Park, Hyun Woo
AU - Jewell, Jenna L.
AU - Chen, Qian
AU - Deng, Yaoting
AU - Pan, Duojia
AU - Taylor, Susan S.
AU - Lai, Zhi Chun
AU - Guan, Kun Liang
PY - 2013/2/1
Y1 - 2013/2/1
N2 - The Hippo tumor suppressor pathway plays an important role in tissue homeostasis that ensures development of functional organs at proper size. The YAP transcription coactivator is a major effector of the Hippo pathway and is phosphorylated and inactivated by the Hippo pathway kinases Lats1/2. It has recently been shown that YAP activity is regulated by G-protein-coupled receptor signaling. Here we demonstrate that cyclic adenosine monophosphate (cAMP), a second messenger downstream from Gas-coupled receptors, acts through protein kinase A (PKA) and Rho GTPases to stimulate Lats kinases and YAP phosphorylation. We also show that inactivation of YAP is crucial for PKA-induced adipogenesis. In addition, PKA activation in Drosophila inhibits the expression of Yorki (Yki, a YAP ortholog) target genes involved in cell proliferation and death. Taken together, our study demonstrates that Hippo-YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions.
AB - The Hippo tumor suppressor pathway plays an important role in tissue homeostasis that ensures development of functional organs at proper size. The YAP transcription coactivator is a major effector of the Hippo pathway and is phosphorylated and inactivated by the Hippo pathway kinases Lats1/2. It has recently been shown that YAP activity is regulated by G-protein-coupled receptor signaling. Here we demonstrate that cyclic adenosine monophosphate (cAMP), a second messenger downstream from Gas-coupled receptors, acts through protein kinase A (PKA) and Rho GTPases to stimulate Lats kinases and YAP phosphorylation. We also show that inactivation of YAP is crucial for PKA-induced adipogenesis. In addition, PKA activation in Drosophila inhibits the expression of Yorki (Yki, a YAP ortholog) target genes involved in cell proliferation and death. Taken together, our study demonstrates that Hippo-YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions.
KW - Adipogenesis
KW - Hippo
KW - PKA
KW - Proliferation
KW - YAP
UR - http://www.scopus.com/inward/record.url?scp=84878868616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878868616&partnerID=8YFLogxK
U2 - 10.1101/gad.219402.113
DO - 10.1101/gad.219402.113
M3 - Article
C2 - 23752589
AN - SCOPUS:84878868616
VL - 27
SP - 1223
EP - 1232
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 11
ER -