Featured Research

from universities, journals, and other organizations

Scientists discover Par-1 as a new component of the Hippo signaling pathway

Date:
August 6, 2013
Source:
Public Library of Science
Summary:
In the development of animals, which is closely controlled by diverse pathways, the regulation of organ size has been a long-standing puzzle. How does an organ ascertain its optimum size? What are the molecular mechanisms that stop organ growth at an appropriate point during development or regeneration? Almost a decade ago, the discovery of the Hippo signaling pathway provided an important starting point for answering these questions.

In the development of animals, which is closely controlled by diverse pathways, the regulation of organ size has been a long-standing puzzle. How does an organ ascertain its optimum size? What are the molecular mechanisms that stop organ growth at an appropriate point during development or regeneration? Almost a decade ago, the discovery of the Hippo signaling pathway provided an important starting point for answering these questions.

Related Articles


Now, a team of scientists led by Lei Zhang at the Shanghai Institute of Biochemistry & Cell Biology, Chinese Academy of Sciences, has identified a novel component of this pathway, which influences the Hippo protein's phosphorylation status and Hippo-Salvador (another key component of this pathway) association to negatively regulate Hippo kinase activity. Their findings will be published in the open access journal PLOS Biology.

The Hippo pathway regulates organ growth by controlling cell numbers in that organ through the inhibition of the transcriptional coactivator, Yorkie, by a series of phosphorylation events. To initiate these phosphorylation events, the Hippo kinase needs to be phosphorylated on the Thr195 site. Without inhibition from Hippo signaling, Yorkie translocates into the nucleus to bind with transcription factors to induce the expression of specific genes that promote proliferation and inhibit apoptosis. Extensive research has been focused on the study of inappropriate overgrowth induced by Yorkie activity, which is believed to be related to human cancers.

However, the mechanisms that restrict Hippo kinase activity, which results in increased apoptosis and reduced tissue growth, remain unclear. In particular, the identity of the kinase that antagonizes Hippo remains unknown. To help elucidate these mechanisms, the Zhang group performed a gain-of-function screen in Drosophila melanogaster to identify the negative regulators of the Hippo pathway. After screening more than 10,000 lines, they found that Par-1, a multifunctional serine/threonine kinase, promotes organ growth by affecting the Hippo signaling pathway.

Dr. Lei Zhang and his colleagues demonstrated that Par-1 physically interacts with Hippo and its scaffold protein, Salvador. Using biochemical approaches, they were able to show that Par-1 regulates the phosphorylation of Hippo at Ser30 and promotes the dissociation of Salvador from the Hippo-Salvador complex, eventually resulting in Salvador dephosphorylation and destabilization. "How the activity of Hippo is regulated is fascinating to all scientists in this field. Our studies provide the first-hand evidence that, besides the well-known Thr195 autophosphorylation site, Hippo's activity can be affected by another phosphorylation site," said first author Hongling Huang.

"With this new understanding of how Par-1 regulates Hippo activity and prevents inappropriate Hippo activation, our knowledge of the Hippo signaling network has greatly expanded. As the function of Par-1 in regulating Hippo signaling is evolutionarily conserved, our studies also suggest Par-1 plays a role in carcinogenesis," added Dr. Lei Zhang. "Considering that Par-1 is a well-known polarity regulator, we'd like to focus on exploring the relationship between the Hippo pathway and the polarity components in the future."


Story Source:

The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hong-Ling Huang, Shimin Wang, Meng-Xin Yin, Liang Dong, Chao Wang, Wei Wu, Yi Lu, Miao Feng, Chuanyang Dai, Xiaocan Guo, Li Li, Bin Zhao, Zhaocai Zhou, Hongbin Ji, Jin Jiang, Yun Zhao, Xin-Yuan Liu, Lei Zhang. Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biology, 2013; 11 (8): e1001620 DOI: 10.1371/journal.pbio.1001620

Cite This Page:

Public Library of Science. "Scientists discover Par-1 as a new component of the Hippo signaling pathway." ScienceDaily. ScienceDaily, 6 August 2013. <www.sciencedaily.com/releases/2013/08/130806203503.htm>.
Public Library of Science. (2013, August 6). Scientists discover Par-1 as a new component of the Hippo signaling pathway. ScienceDaily. Retrieved January 26, 2015 from www.sciencedaily.com/releases/2013/08/130806203503.htm
Public Library of Science. "Scientists discover Par-1 as a new component of the Hippo signaling pathway." ScienceDaily. www.sciencedaily.com/releases/2013/08/130806203503.htm (accessed January 26, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Monday, January 26, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How To: Mixed Green Salad Topped With Camembert Cheese

How To: Mixed Green Salad Topped With Camembert Cheese

Rumble (Jan. 26, 2015) Learn how to make a mixed green salad topped with a pan-seared camembert cheese in only a minute! Music: Courtesy of Audio Network. Video provided by Rumble
Powered by NewsLook.com
Water Fleas Prepare for Space Voyage

Water Fleas Prepare for Space Voyage

Reuters - Innovations Video Online (Jan. 26, 2015) Scientists are preparing a group of water fleas for a unique voyage into space. The aquatic crustaceans, known as Daphnia, can be used as a miniature model for biomedical research, and their reproductive and swimming behaviour will be tested for signs of stress while on board the International Space Station. Jim Drury went to meet the team. Video provided by Reuters
Powered by NewsLook.com
Husky Puppy Plays With Ferret

Husky Puppy Plays With Ferret

Rumble (Jan. 26, 2015) It looks like this 2-month-old Husky puppy and the family ferret are going to be the best of friends. Look at how much fun they&apos;re having together! Credit to &apos;Vira&apos;. Video provided by Rumble
Powered by NewsLook.com
Scientists Model Flying, Walking Drone After Vampire Bats

Scientists Model Flying, Walking Drone After Vampire Bats

Buzz60 (Jan. 26, 2015) Swiss scientists build a new drone that can both fly and walk, modeling it after the movements of common vampire bats. Jen Markham (@jenmarkham) has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins