scholarly journals Dorsal Ruffle Microdomains Potentiate Met Receptor Tyrosine Kinase Signaling and Down-regulation

2010 ◽  
Vol 285 (32) ◽  
pp. 24956-24967 ◽  
Author(s):  
Jasmine V. Abella ◽  
Christine A. Parachoniak ◽  
Veena Sangwan ◽  
Morag Park
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Kinase Signaling ◽  
Met Receptor ◽  
Down Regulation ◽  
Tyrosine Kinase Signaling ◽  
Met Receptor Tyrosine Kinase

scholarly journals Met Receptor Tyrosine Kinase Signaling Induces Secretion of the Angiogenic Chemokine Interleukin-8/CXCL8 in Pancreatic Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40420 ◽  
Author(s):  
Kristen S. Hill ◽  
Ivana Gaziova ◽  
Lindsay Harrigal ◽  
Yvette A. Guerra ◽  
Suimin Qiu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Interleukin 8 ◽  
Kinase Signaling ◽  
Met Receptor ◽  
Tyrosine Kinase Signaling ◽  
Met Receptor Tyrosine Kinase

scholarly journals Down-Regulation of the Met Receptor Tyrosine Kinase by Presenilin-dependent Regulated Intramembrane Proteolysis

2009 ◽  
Vol 20 (9) ◽  
pp. 2495-2507 ◽  
Author(s):  
Bénédicte Foveau ◽  
Frédéric Ancot ◽  
Catherine Leroy ◽  
Annalisa Petrelli ◽  
Karina Reiss ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Invasive Growth ◽  
Met Receptor ◽  
Inhibitory Antibody ◽  
Down Regulation ◽  
Intramembrane Proteolysis ◽  
Regulated Intramembrane Proteolysis ◽  
Met Receptor Tyrosine Kinase

Hepatocyte growth factor/scatter factor (HGF/SF) acts through the membrane-anchored Met receptor tyrosine kinase to induce invasive growth. Deregulation of this signaling is associated with tumorigenesis and involves, in most cases, overexpression of the receptor. We demonstrate that Met is processed in epithelial cells by presenilin-dependent regulated intramembrane proteolysis (PS-RIP) independently of ligand stimulation. The proteolytic process involves sequential cleavage by metalloproteases and the γ-secretase complex, leading to generation of labile fragments. In normal epithelial cells, although expression of cleavable Met by PS-RIP is down-regulated, uncleavable Met displayed membrane accumulation and induced ligand-independent motility and morphogenesis. Inversely, in transformed cells, the Met inhibitory antibody DN30 is able to promote Met PS-RIP, resulting in down-regulation of the receptor and inhibition of the Met-dependent invasive growth. This demonstrates the original involvement of a proteolytic process in degradation of the Met receptor implicated in negative regulation of invasive growth.

Sign in / Sign up

Export Citation Format

Share Document