Cell adhesion to the extracellular matrix or to surrounding cells plays a key role in cell proliferation and differentiation and is critical for proper tissue homeostasis. An important pathway in adhesion-dependent cell proliferation is the Hippo signaling cascade, which is coregulated by the transcription factors Yes-associated protein 1 (YAP1) and transcriptional coactivator with PDZ-binding motif (TAZ). However, how cells integrate extracellular information at the molecular level to regulate YAP1's nuclear localization is still puzzling. Herein, we investigated the role of β1 integrins in regulating this process. We found that β1 integrin–dependent cell adhesion is critical for supporting cell proliferation in mesenchymal cells both in vivo and in vitro. β1 integrin–dependent cell adhesion relied on the relocation of YAP1 to the nucleus after the down-regulation of its phosphorylated state mediated by large tumor suppressor gene 1 and 2 (LATS1/2). We also found that this phenotype relies on β1 integrin–dependent local activation of the small GTPase RAC1 at the plasma membrane to control the activity of P21 (RAC1)-activated kinase (PAK) of group 1. We further report that the regulatory protein merlin (neurofibromin 2, NF2) interacts with both YAP1 and LATS1/2 via its C-terminal moiety and FERM domain, respectively. PAK1-mediated merlin phosphorylation on Ser-518 reduced merlin's interactions with both LATS1/2 and YAP1, resulting in YAP1 dephosphorylation and nuclear shuttling. Our results highlight RAC/PAK1 as major players in YAP1 regulation triggered by cell adhesion.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ArPZ9I
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
-
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
-
Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
-
2016-11-22T07-55-59Z Source: International Journal of Medical Science and Public Health Banothu Srinivas, Madhu Mohan Reddy B. Backgrou...
-
2016-10-15T06-30-01Z Source: The Southeast Asian Journal of Case Report and Review Sangita Deepak Kamath, Neeraj Jain, Saurabh Pathak, Ba...
-
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with cl...
-
Abstract The development of focused ion beam-scanning electron microscopy (FIB-SEM) techniques has allowed high-resolution 3D imaging of n...
-
Vol.48 No.2 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1S2Z7n2 via IFTTT
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου