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PMID:19520808
| Citation |
Ghosh, MC, Collins, GD, Vandanmagsar, B, Patel, K, Brill, M, Carter, A, Lustig, A, Becker, KG, Wood, WW 3rd, Emeche, CD, French, AD, O'Connell, MP, Xu, M, Weeraratna, AT and Taub, DD (2009) Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration. Blood 114:1366-73 |
|---|---|
| Abstract |
Chemokines mediate the signaling and migration of T cells, but little is known about the transcriptional events involved therein. Microarray analysis of CXC chemokine ligand (CXCL) 12-treated T cells revealed that Wnt ligands are significantly up-regulated during CXCL12 treatment. Real-time polymerase chain reaction and Western blot analysis confirmed that the expression of noncanonical Wnt pathway members (eg, Wnt5A) was specifically up-regulated during CXCL12 stimulation, whereas beta-catenin and canonical Wnt family members were selectively down-regulated. Wnt5A augmented signaling through the CXCL12-CXCR4 axis via the activation of protein kinase C. Moreover, Wnt5A expression was required for CXCL12-mediated T-cell migration, and rWnt5A sensitized human T cells to CXCL12-induced migration. Furthermore, Wnt5A expression was also required for the sustained expression of CXCR4. These results were further supported in vivo using EL4 thymoma metastasis as a model of T-cell migration. Together, these data demonstrate that Wnt5A is a critical mediator of CXCL12-CXCR4 signaling and migration in human and murine T cells. |
| Links |
PubMed PMC2727408 Online version:10.1182/blood-2008-08-175869 |
| Keywords |
Animals; Cell Line, Tumor; Cell Movement/genetics; Cell Movement/immunology; Chemokine CXCL12/genetics; Chemokine CXCL12/immunology; Chemokine CXCL12/metabolism; Humans; Mice; Mice, Mutant Strains; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/immunology; Proto-Oncogene Proteins/metabolism; Receptors, CXCR4/genetics; Receptors, CXCR4/immunology; Receptors, CXCR4/metabolism; Signal Transduction/genetics; Signal Transduction/immunology; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; Up-Regulation/genetics; Up-Regulation/immunology; Wnt Proteins/genetics; Wnt Proteins/immunology; Wnt Proteins/metabolism; beta Catenin/genetics; beta Catenin/immunology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0032722: positive regulation of chemokine production |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0010820: positive regulation of T cell chemotaxis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0045080: positive regulation of chemokine biosynthetic process |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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