Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0001511 (
Adhesion
)
5,955
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cell migration requires the cyclical assembly and disassembly of focal adhesions.
Adhesion
induces phosphorylation of focal adhesion proteins, including Cas (Crk-associated substrate/p130Cas/BCAR1). However, Cas phosphorylation stimulates adhesion turnover. This raises the question of how adhesion assembly occurs against opposition from phospho-Cas. Here we show that
suppressor of cytokine signaling 6
(
SOCS6
) and Cullin 5, two components of the CRL5
SOCS6
ubiquitin ligase, inhibit Cas-dependent focal adhesion turnover at the front but not rear of migrating epithelial cells. The front focal adhesions contain phospho-Cas which recruits
SOCS6
. If
SOCS6
cannot access focal adhesions, or if cullins or the proteasome are inhibited, adhesion disassembly is stimulated. This suggests that the localized targeting of phospho-Cas within adhesions by CRL5
SOCS6
and concurrent cullin and proteasome activity provide a negative feedback loop, ensuring that adhesion assembly predominates over disassembly at the leading edge. By this mechanism, ubiquitination provides a new level of spatio-temporal control over cell migration.
...
PMID:The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells. 2765 5
