Truncation of C-mip (Tc-mip), a new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization.
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 gamma 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.
Grimbert
Philippe
P
Unité INSERM 99, Hôpital Henri Mondor, AP-HP, Université Paris XII, 51 avenue du Marechal de Lattre-de-Tassigny, 94010 Créteil, France.
Valanciute
Asta
A
Audard
Vincent
V
Pawlak
André
A
Le gouvelo
Sabine
S
Lang
Philippe
P
Niaudet
Patrick
P
Bensman
Albert
A
Guellaën
Georges
G
Sahali
Djillali
D
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001483:Base Sequence; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051257:Proto-Oncogene Proteins c-maf; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; C540426:CMIP protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C495607:MAF protein, human; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D011994:Recombinant Proteins; D014157:Transcription Factors