Reciprocal raft–receptor interactions and the assembly of adhesion complexes

Harris, Tony; Siu, Chi‐Hung

doi:10.1002/bies.10172

Cited by 78 publications

(59 citation statements)

References 87 publications

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“…GPI-anchored proteins are known to exist in clusters and form microdomains at the surface of the plasma membrane, referred to as "lipid rafts" (8). These microdomains appear to be important for GPI-anchored protein signal transduction.…”

Section: Ceacam6mentioning

confidence: 99%

CEACAM6 Cross-linking Induces Caveolin-1-dependent, Src-mediated Focal Adhesion Kinase Phosphorylation in BxPC3 Pancreatic Adenocarcinoma Cells

Duxbury

Ito

Ashley

et al. 2004

Journal of Biological Chemistry

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Despite lacking transmembrane or intracellular domains, glycosylphosphatidylinositol-anchored proteins can modulate intracellular signaling events, in many cases through aggregation within membrane "lipid raft" microdomains. CEACAM6 is a glycosylphosphatidylinositol-linked cell surface protein of importance in the anchorage-independent survival and metastasis of pancreatic adenocarcinoma cells. We examined the effects of antibody-mediated cross-linking of CEACAM6 on intracellular signaling events and anchorage-independent survival of the CEACAM6-overexpressing pancreatic ductal adenocarcinoma cell line, BxPC3. CEACAM6 cross-linking increased c-Src activation and induced tyrosine phosphorylation of p125 FAK focal adhesion kinase. Focal adhesion kinase phosphorylation was dependent on c-Src kinase activation, for which caveolin-1 was required. CEACAM6 cross-linking induced a significant increase in cellular resistance to anoikis. These observations represent the first characterization of the mechanism through which this important cell surface oncoprotein influences intracellular signaling events and hence malignant cellular behavior. CEACAM61 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein that is overexpressed in a variety of human malignancies, including pancreatic adenocarcinoma (1, 2). This immunoglobulin superfamily member is emerging as an important determinant of a variety of aspects of the malignant cellular phenotype (1-3). We reported previously that levels of CEACAM6 expression modulate the susceptibility of pancreatic adenocarcinoma cells to anoikis (2). Normal epithelial cells require anchorage to an extracellular matrix for growth, survival, and differentiation. Resistance to anoikis, a subset of apoptosis induced by inadequate or inappropriate cell-substrate contact in normal cells, is a property of transformed cells that is associated with enhanced tumorigenesis and metastatic ability. Despite clear indications of its important role in cancer cell biology, the mechanisms through which CEACAM6 influences intracellular signal transduction remain poorly understood.Despite lacking transmembrane and intracellular domains, several GPI-anchored proteins, including CEACAM family members, are able to influence intracellular events and have been implicated in transmembrane signaling via tyrosine kinases (4 -7). GPI-anchored proteins are known to exist in clusters and form microdomains at the surface of the plasma membrane, referred to as "lipid rafts" (8). These microdomains appear to be important for GPI-anchored protein signal transduction. A number of signal transduction components, including Src family tyrosine kinases, are associated with lipid rafts, and cross-linking of cell surface molecules by a variety of techniques has proven to be a useful tool for exploring the functional roles of raft-associated proteins (9 -14).Here, we examine the effects of antibody-mediated crosslinking of CEACAM6 in pancreatic adenocarcinoma cells. We determine the effects of CEACAM6 cross-linking on ...

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Section: Ceacam6mentioning

confidence: 99%

CEACAM6 Cross-linking Induces Caveolin-1-dependent, Src-mediated Focal Adhesion Kinase Phosphorylation in BxPC3 Pancreatic Adenocarcinoma Cells

Duxbury

Ito

Ashley

et al. 2004

Journal of Biological Chemistry

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“…The effects of Ca 2ϩ signaling on HA-induced EC barrier regulation are currently under investigation. Caveolin-enriched microdomains or lipid rafts, are important plasma membrane microdomains that regulate numerous EC functions (45,46). CD44 localization in lipid rafts is important for HA-mediated signaling (21,30) as cholesterol depletion blocks both low and high MW HA-induced EC barrier responses.…”

Section: Discussionmentioning

confidence: 99%

Transactivation of Sphingosine 1-Phosphate Receptors Is Essential for Vascular Barrier Regulation

Singleton

Dudek

Fan

et al. 2006

Journal of Biological Chemistry

173

221

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The role for hyaluronan (HA) and CD44 in vascular barrier regulation is unknown. We examined high and low molecular weight HA (HMW-HA, ϳ1,000 kDa; LMW-HA, ϳ2.5 kDa) effects on human transendothelial monolayer electrical resistance (TER). HMW-HA increased TER, whereas LMW-HA induced biphasic TER changes ultimately resulting in EC barrier disruption. HMW-HA induced the association of the CD44s isoform with, and AKT-mediated phosphorylation of, the barrierpromoting sphingosine 1-phosphate receptor (S1P 1 ) within caveolin-enriched lipid raft microdomains, whereas LMW-HA induced brief CD44s association with S1P 1 followed by sustained association of the CD44v10 isoform with, and Src and ROCK 1/2-mediated phosphorylation of, the barrier-disrupting S1P 3 receptor. HA-induced EC cytoskeletal reorganization and TER alterations were abolished by either disruption of lipid raft formation, CD44 blocking antibody or siRNA-mediated reductions in expression of CD44 isoforms. Silencing S1P 1 , AKT1, or Rac1 blocked the barrier enhancing effects of HA whereas silencing S1P 3 , Src, ROCK1/2, or RhoA blocked the barrier disruption induced by LMW-HA. In summary, HA regulates EC barrier function through novel differential CD44 isoform interaction with S1P receptors, S1P receptor transactivation, and RhoA/Rac1 signaling to the EC cytoskeleton.

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“…Recently, the concept of "lipid rafts," or specialized membrane lipid microdomains, has been suggested as a mechanism whereby signaling, trafficking, and the assembly of adhesion complexes takes place (Brown and London, 2000;Simons and Toomre, 2000;Harris and Siu, 2002), although dissenting views have been offered (Munro, 2003). Neuronal and myelin membranes may have several kinds of rafts, because various proteins can segregate into biochemically distinct entities depending on the experimental and physiological conditions (Madore et al, 1999;Hakomori, 2002;Taylor et al, 2002;Marta et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Does Paranode Formation and Maintenance Require Partitioning of Neurofascin 155 into Lipid Rafts?

Schafer¹,

Bansal²,

Hedstrom³

et al. 2004

J. Neurosci.

125

157

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Paranodal axoglial junctions in myelinated nerve fibers are essential for efficient action potential conduction and ion channel clustering. We show here that, in the mature CNS, a fraction of the oligodendroglial 155 kDa isoform of neurofascin (NF-155), a major constituent of paranodal junctions, has key biochemical characteristics of a lipid raft-associated protein. However, despite its robust expression, NF-155 is detergent soluble before paranodes form and in purified oligodendrocyte cell cultures. Only during its progressive localization to paranodes is NF-155 (1) associated with detergent-insoluble complexes that float at increasingly lower densities of sucrose and (2) retained in situ after detergent treatment. Finally, mutant animals with disrupted paranodal junctions, including those lacking specific myelin lipids, have significantly reduced levels of raft-associated NF-155. Together, these results suggest that trans interactions between oligodendroglial NF-155 and axonal ligands result in cross-linking, stabilization, and formation of paranodal lipid raft assemblies.

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Reciprocal raft–receptor interactions and the assembly of adhesion complexes

Cited by 78 publications

References 87 publications

CEACAM6 Cross-linking Induces Caveolin-1-dependent, Src-mediated Focal Adhesion Kinase Phosphorylation in BxPC3 Pancreatic Adenocarcinoma Cells

CEACAM6 Cross-linking Induces Caveolin-1-dependent, Src-mediated Focal Adhesion Kinase Phosphorylation in BxPC3 Pancreatic Adenocarcinoma Cells

Transactivation of Sphingosine 1-Phosphate Receptors Is Essential for Vascular Barrier Regulation

Does Paranode Formation and Maintenance Require Partitioning of Neurofascin 155 into Lipid Rafts?

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