Linked Life Data

19632321

Source:http://linkedlifedata.com/resource/pubmed/id/19632321

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-8-31
pubmed:abstractText
Cdc42-Interacting Protein-4 (CIP4) family adaptors have been implicated in promoting Epidermal Growth Factor Receptor (EGFR) internalization, however, their unique or overlapping functions remain unclear. Here, we show that although CIP4 was not required for early events in clathrin-mediated endocytosis of EGFR, CIP4 localizes to vesicles containing EGFR and Rab5. Furthermore, expression of constitutively active Rab5 led to accumulation of CIP4 and the related adaptor Toca-1 in giant endosomes. Using a mutagenesis approach, we show that localization of CIP4 to endosomes is mediated in part via the curved phosphoinositide-binding face of the CIP4 F-BAR domain. Downregulation of CIP4 in A431 epidermoid carcinoma cells by RNA interference led to elevated EGFR levels, compared to control cells. Although surface expression of EGFR was not affected by CIP4 silencing, EGF-induced transit of EGFR from EEA1-positive endosomes to lysosomes was reduced compared to control cells. This correlated with more robust activation of ERK kinase and entry to S phase in CIP4-depleted A431 cells, compared to control cells. The combined silencing of CIP4 and Toca-1 was more effective in driving cells into S phase, suggesting a partial redundancy in their functions. Overall, our results implicate CIP4 and Toca-1 in regulating late events in EGFR trafficking from endosomes that serves to limit sustained ERK activation within the endosomal compartment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1873-3913
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1686-97
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
F-BAR-containing adaptor CIP4 localizes to early endosomes and regulates Epidermal Growth Factor Receptor trafficking and downregulation.
pubmed:affiliation
Queen's University Cancer Research Institute, Division of Cancer Biology & Genetics and Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't