Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis.

J Biol Chem

Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address:

Published: November 2013

The Hippo tumor suppressor pathway plays important roles in organ size control through Lats1/2 mediated phosphorylation of the YAP/TAZ transcription co-activators. However, YAP/TAZ independent functions of the Hippo pathway are largely unknown. Here we report a novel role of the Hippo pathway in angiogenesis. Angiomotin p130 isoform (AMOTp130) is phosphorylated on a conserved HXRXXS motif by Lats1/2 downstream of GPCR signaling. Phosphorylation disrupts AMOT interaction with F-actin and correlates with reduced F-actin stress fibers and focal adhesions. Furthermore, phosphorylation of AMOT by Lats1/2 inhibits endothelial cell migration in vitro and angiogenesis in zebrafish embryos in vivo. Thus AMOT is a direct substrate of Lats1/2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837143PMC
http://dx.doi.org/10.1074/jbc.M113.518019DOI Listing

Publication Analysis

Top Keywords

cell migration
12
hippo pathway
12
migration angiogenesis
8
functions hippo
8
endothelial cell
8
lats1/2
5
phosphorylation
4
phosphorylation angiomotin
4
angiomotin lats1/2
4
lats1/2 kinases
4

Similar Publications

Background: Pancreatic adenocarcinoma (PAAD) is a common malignancy with a very low survival rate. More and more studies have shown that SPTAN1 may be involved in the development and progression of a variety of tumors, including rectal cancer, Pancreatic adenocarcinoma, etc., and may affect their prognosis.

View Article and Find Full Text PDF

Osteosarcoma (OS) is a prevalent invasive bone cancer, with numerous homeobox family genes implicated in tumor progression. This study aimed to develop a prognostic model using HOX family genes to assess osteosarcoma patient outcomes. Data from osteosarcoma patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were collected.

View Article and Find Full Text PDF

De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB. Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling.

View Article and Find Full Text PDF

Inflammation is a dynamic process which importantly involves migration of immune cells. Understanding the onset, acute phase and resolution of inflammation is greatly facilitated by their imaging. However, immune cells are sensitive, difficult to genetically manipulate and prone to changes in response to contact, hindering the application of well-established cell labeling methods.

View Article and Find Full Text PDF

Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors.

J Immunother Cancer

January 2025

Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, People's Republic of China

Background: Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors.

Methods: In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto the adoptive T cell surface via bioorthogonal reactions, aiming to specifically inhibit the group IVA cytosolic phospholipase Aα (cPLAα), a key enzyme facilitating phospholipid metabolism and senescent state of T cells.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!