Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association.
The evolutionarily conserved Hippo (Hpo) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death. Here, we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster. Overexpression of Par-1 elevated Yorkie activity, resulting in increased Hpo target gene expression and tissue overgrowth, while loss of Par-1 diminished Hpo target gene expression and reduced organ size. We demonstrated that par-1 functioned downstream of fat and expanded and upstream of hpo and salvador (sav). In addition, we also found that Par-1 physically interacted with Hpo and Sav and regulated the phosphorylation of Hpo at Ser30 to restrict its activity. Par-1 also inhibited the association of Hpo and Sav, resulting in Sav dephosphorylation and destabilization. Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network.
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P.R. China.
Hong-Ling
HL
Huang
Shimin
S
Wang
Meng-Xin
MX
Yin
Liang
L
Dong
Chao
C
Wang
Wei
W
Wu
Yi
Y
Lu
Miao
M
Feng
Chuanyang
C
Dai
Xiaocan
X
Guo
Li
L
Li
Bin
B
Zhao
Zhaocai
Z
Zhou
Hongbin
H
Ji
Jin
J
Jiang
Yun
Y
Zhao
Xin-Yuan
XY
Liu
Lei
L
Zhang
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099317:Hippo Kinases
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D044463:Receptor, PAR-1; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases