5 research outputs found
Phosphoinositide 3-kinase signaling pathway mediated by p110α regulates invadopodia formation
Inhibition of p110α or of the downstream PI3K signaling pathway components PDK1 and Akt, as well as phosphoinositide sequestration, blocks invadopodia formation in breast cancer cells
p120 Catenin Recruits Cadherins to γ-Secretase and Inhibits Production of Aβ Peptide*S⃞
The γ-secretase complex cleaves many transmembrane proteins,
including amyloid precursor protein, EphB and ErbB tyrosine kinase receptors,
Notch1 receptors, and adhesion factors. Presenilin 1, the catalytic subunit of
γ-secretase, associates with the cadherin/catenin cell-cell
adhesion/communication system and promotes cadherin processing
(Georgakopoulos, A., et al. (1999) Mol. Cell 4,
893–902; Marambaud, P., et al. (2002) EMBO J. 21,
1948–1956), but the mechanism by which γ-secretase and cadherins
associate is unclear. Here we report that p120 catenin (p120ctn), a component
of the cadherin-catenin complex, recruits γ-secretase to cadherins, thus
stimulating their processing while inhibiting production of Aβ peptide
and the amyloid precursor protein intracellular domain. This function of
p120ctn depends on both p120ctn-cadherin and p120ctn-presenilin 1 binding,
indicating that p120ctn is the central factor that bridges γ-secretase
and cadherin-catenin complexes. Our data show that p120ctn is a unique
positive regulator of the γ-secretase processing of cadherins and a
negative regulator of the amyloid precursor protein processing. Furthermore,
our data suggest that specific members of the γ-secretase complex may be
used to recruit different substrates and that distinct PS1 sequences are
required for processing of APP and cadherins