Truncation of C-mip (Tc-mip), a New Proximal Signaling Protein, Induces c-maf Th2 Transcription Factor and Cytoskeleton Reorganization
Open Access
- 25 August 2003
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 198 (5), 797-807
- https://doi.org/10.1084/jem.20030566
Abstract
Several arguments suggest that minimal change nephrotic syndrome (MCNS) results from yet unknown systemic disorder of T cell function. By screening a cDNA library from T cell relapse, we identified a new pleckstrin homology (PH) domain-containing protein encoded by a gene located on chromosome 16q24. Two alternative transcripts were identified. The first species (c-mip) was expressed in fetal liver, kidney, and peripheral blood mononuclear cells (PBMCs), but weakly detected in PBMCs from MCNS patients. The second form (Tc-mip, standing for truncated c-maf inducing protein), corresponds to subtracted transcript and lacks the NH2-terminal PH domain. The expression of Tc-mip was restricted to fetal liver, thymus, and MCNS PBMCs where it was specifically recruited in CD4+ T cells subset. Overexpression of Tc-mip in T cell Jurkat induced c-maf, transactivated the interleukin 4 gene and down-regulated the interferon γ expression, characteristic of a Th2 commitment. Moreover, the overexpression of Tc-mip induced Src phosphorylation, T cell clustering, and a cellular redistribution of the cytoskeleton-associated L-plastin, by a PI3 kinase independent pathway. Tc-mip represents therefore the first identified protein, which links proximal signaling to c-maf induction.Keywords
This publication has 44 references indexed in Scilit:
- RANTES Production by Memory Phenotype T Cells Is Controlled by a Posttranscriptional, TCR-Dependent ProcessImmunity, 2002
- Transcription: Tantalizing Times for T CellsCell, 2002
- Itk/Emt: a link between T cell antigen receptor-mediated Ca2+ events and cytoskeletal reorganizationTrends in Immunology, 2001
- Interleukin-12 and interferon-γ production in childhood idiopathic nephrotic syndromePediatric Nephrology, 1998
- The Proto-Oncogene c-maf Is Responsible for Tissue-Specific Expression of Interleukin-4Cell, 1996
- Protein modules and signalling networksNature, 1995
- Modular binding domains in signal transduction proteinsCell, 1995
- Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphateNature, 1994
- Nephrotic syndrome in childrenCurrent Opinion in Pediatrics, 1993
- The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone: A report of the international study of kidney disease in childrenThe Journal of Pediatrics, 1981