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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2004-10-19
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pubmed:abstractText |
The cancer metastasis suppressor protein KAI1/CD82 is a member of the tetraspanin superfamily. Recent studies have demonstrated that tetraspanins are palmitoylated and that palmitoylation contributes to the organization of tetraspanin webs or tetraspanin-enriched microdomains. However, the effect of palmitoylation on tetraspanin-mediated cellular functions remains obscure. In this study, we found that tetraspanin KAI1/CD82 was palmitoylated when expressed in PC3 metastatic prostate cancer cells and that palmitoylation involved all of the cytoplasmic cysteine residues proximal to the plasma membrane. Notably, the palmitoylation-deficient KAI1/CD82 mutant largely reversed the wild-type KAI1/CD82's inhibitory effects on migration and invasion of PC3 cells. Also, palmitoylation regulates the subcellular distribution of KAI1/CD82 and its association with other tetraspanins, suggesting that the localized interaction of KAI1/CD82 with tetraspanin webs or tetraspanin-enriched microdomains is important for KAI1/CD82's motility-inhibitory activity. Moreover, we found that KAI1/CD82 palmitoylation affected motility-related subcellular events such as lamellipodia formation and actin cytoskeleton organization and that the alteration of these processes likely contributes to KAI1/CD82's inhibition of motility. Finally, the reversal of cell motility seen in the palmitoylation-deficient KAI1/CD82 mutant correlates with regaining of p130(CAS)-CrkII coupling, a signaling step important for KAI1/CD82's activity. Taken together, our results indicate that palmitoylation is crucial for the functional integrity of tetraspanin KAI1/CD82 during the suppression of cancer cell migration and invasion.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD82,
http://linkedlifedata.com/resource/pubmed/chemical/BCAR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bcar1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bcar1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/CD82 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cd82 antigen, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cd82 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Crk protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Crk-Associated Substrate Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Palmitates,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-crk,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma-Like Protein p130
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
64
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7455-63
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15492270-Animals,
pubmed-meshheading:15492270-Antigens, CD,
pubmed-meshheading:15492270-Antigens, CD82,
pubmed-meshheading:15492270-Cell Line, Tumor,
pubmed-meshheading:15492270-Cell Movement,
pubmed-meshheading:15492270-Crk-Associated Substrate Protein,
pubmed-meshheading:15492270-Humans,
pubmed-meshheading:15492270-Male,
pubmed-meshheading:15492270-Membrane Glycoproteins,
pubmed-meshheading:15492270-Mice,
pubmed-meshheading:15492270-Neoplasm Metastasis,
pubmed-meshheading:15492270-Palmitates,
pubmed-meshheading:15492270-Prostatic Neoplasms,
pubmed-meshheading:15492270-Proteins,
pubmed-meshheading:15492270-Proto-Oncogene Proteins,
pubmed-meshheading:15492270-Proto-Oncogene Proteins c-crk,
pubmed-meshheading:15492270-Rats,
pubmed-meshheading:15492270-Retinoblastoma-Like Protein p130,
pubmed-meshheading:15492270-Subcellular Fractions,
pubmed-meshheading:15492270-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity.
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pubmed:affiliation |
Vascular Biology Center and Department of Medicine and Department of Molecular Science, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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