© 2005 The Japanese Biochemical Society
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Selective Inhibition of Fc
RI-Mediated Mast Cell Activation by a Truncated Variant of Cbl-b Related to the Rat Model of Type 1 Diabetes Mellitus
1 Division of Proteomics and 2 Division of Microbiology, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017
To whom correspondence should be addressed. Phone: +81-78-382-5501, Fax: +81-78-382-5519, E-mail: ksada{at}med.kobe-u.ac.jp
Ubiquitin-protein ligase Cbl-b negatively regulates high affinity IgE receptor (Fc
RI)–mediated degranulation and cytokine gene transcription in mast cells. In this study, we have examined the role of a truncated variant of Cbl-b related to the rat model of type 1 diabetes mellitus using the mast cell signaling model. Overexpression of the truncated Cbl-b that lacks the C-terminal region did not suppress the activation of proximal and distal signaling molecules leading to degranulation. FcRI-mediated tyrosine phosphorylation of Syk, Gab2, and phospholipase C-
1, and activation of c-Jun N-terminal kinase (JNK), extracellular signal–regulated kinase (ERK), p38 mitogen–activated protein kinase (MAP kinase), and inhibitor of nuclear factor 
B kinase (IKK), and generation of Rac1 are unaffected in cells overexpressing the truncated Cbl-b in the lipid raft. On the other hand, FcRI-mediated transcriptional activation of nuclear factor of activated T cells (NFAT), and transcription of interleukin-3 (IL-3) and IL-4 mRNA are inhibited by overexpression of the truncated variant of Cbl-b. This suppression parallels the re-compartmentalization of specific effector molecules in the lipid raft. These structural and functional analyses reveal the mechanism underlying the selective inhibition of cellular signaling by the truncated variant of Cbl-b related to insulin-dependent diabetes mellitus.
* On leave from the Registered Dietitian’s Section, Faculty of Home Economics, Kobe Women’s University.
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