Linked Life Data

15668240

Source:http://linkedlifedata.com/resource/pubmed/id/15668240

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2005-3-28
pubmed:abstractText
Phosphoinositide lipid second messengers are integral components of signaling pathways mediated by insulin, growth factors, and integrins. SHIP2 dephosphorylates phosphatidylinositol 3,4,5-trisphosphate generated by the activated phosphatidylinositol 3'-kinase. SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity. SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading. Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2. To better understand SHIP2 function, we employed RNA interference (RNAi) approach to silence the expression of the endogenous SHIP2 in HeLa cells. Suppression of SHIP2 levels caused severe F-actin deformities characterized by weak cortical actin and peripheral actin spikes. SHIP2 RNAi cells displayed cell-spreading defects involving a notable absence of focal contact structures and the formation of multiple slender membrane protrusions capped by actin spikes. Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin. EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase. Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Accordingly, we suggest that, in HeLa cells, SHIP2 plays a distinct role in signaling pathways mediated by integrins and growth factor receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13129-36
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15668240-Actins, pubmed-meshheading:15668240-Blotting, Western, pubmed-meshheading:15668240-Cell Adhesion, pubmed-meshheading:15668240-Cell Line, pubmed-meshheading:15668240-Cell Line, Tumor, pubmed-meshheading:15668240-Cytoplasm, pubmed-meshheading:15668240-Cytoskeleton, pubmed-meshheading:15668240-Down-Regulation, pubmed-meshheading:15668240-Endocytosis, pubmed-meshheading:15668240-Gene Silencing, pubmed-meshheading:15668240-HeLa Cells, pubmed-meshheading:15668240-Humans, pubmed-meshheading:15668240-Immunoprecipitation, pubmed-meshheading:15668240-Insulin, pubmed-meshheading:15668240-Ligands, pubmed-meshheading:15668240-Microscopy, Fluorescence, pubmed-meshheading:15668240-Oncogene Protein v-cbl, pubmed-meshheading:15668240-Phosphatidylinositol 3-Kinases, pubmed-meshheading:15668240-Phosphoric Monoester Hydrolases, pubmed-meshheading:15668240-Protein Binding, pubmed-meshheading:15668240-Protein Structure, Tertiary, pubmed-meshheading:15668240-RNA Interference, pubmed-meshheading:15668240-Receptor, Epidermal Growth Factor, pubmed-meshheading:15668240-Retroviridae Proteins, Oncogenic, pubmed-meshheading:15668240-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15668240-Signal Transduction, pubmed-meshheading:15668240-Time Factors, pubmed-meshheading:15668240-Transfection, pubmed-meshheading:15668240-Tyrosine
pubmed:year
2005
pubmed:articleTitle
SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
pubmed:affiliation
Department of Basic Medical Sciences and Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA. nprasad@purdue.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't