Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly expressed in the immune system

• Published in: Human immunology 2003-04, Vol.64 (4), p.389-401
• Main Authors: Gupta, Sanjay, Lee, Andrea, Hu, Chuanmin, Fanzo, Jessica, Goldberg, Ilan, Cattoretti, Giorgio, Pernis, Alessandra B
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Cell Line, Tumor; Cloning, Molecular; Codon - genetics; DNA, Complementary; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; GEF; Gene Expression; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; Humans; Immune System - metabolism; Interferon Regulatory Factors; Mice; Minor Histocompatibility Antigens; Molecular Sequence Data; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Palatine Tonsil - cytology; Rho GTPases; RNA, Messenger - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; SWAP-70; Transcription Factors - genetics
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/S0198-8859(03)00024-7

Rho GTPases play a fundamental role in a variety of biological processes ranging from the reorganization of the actin cytoskeleton to the regulation of cell proliferation. The activation of Rho GTPases is regulated by guanine nucleotide exchange factors (GEFs) belonging to the Dbl family of proteins. The hallmark of this large family of GEFs is the presence of a tandem DH-PH module in which a pleckstrin-homology (PH) domain is located at the C-terminus of a Dbl-homology (DH) domain. Recent studies have demonstrated that SWAP-70 constitutes a novel class of Rac-GEF, in which the PH domain is located at the N-terminus, rather than the C terminus, of the DH domain. Here we report the molecular cloning of human IBP (IRF-4 binding protein), a new member of this novel family of GEFs. The IBP gene maps to human chromosome 6p21.31 centromeric to the MHC locus. Isolation of the murine IBP cDNA reveals a very high degree of homology with the human IBP cDNA suggesting that IBP is evolutionarily conserved. The 5′ portion of the murine IBP cDNA is furthermore identical to the Def-6 cDNA fragment, which was identified in the course of a search for genes differentially expressed in the murine hematopoietic system. IBP is broadly expressed in the immune system and can be detected in both T and B cell compartments in contrast to SWAP-70 whose expression is primarily restricted to B cells. Taken together these findings indicate that IBP is a novel type of GEF, which participates in the activation of Rho GTPases in lymphoid tissues.