Impaired expression of integrin alpha-4 subunit in cultured mast cells derived from mutant mice of mi/mi genotype.
The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). Because attachment of mi/mi CMCs to fibroblasts is impaired, we examined the expression of integrin genes in mi/mi CMCs in the present study. Among the integrin genes examined, the expression of integrin alpha4 subunit was barely detectable in mi/mi CMCs, and the alpha4 protein was not detected by flow cytometry either. The specific adhesion to vascular cell adhesion molecule-1 (VCAM-1), the ligand for alpha4 subunit, was observed in +/+ CMCs but not in mi/mi CMCs, indicating that the expression of integrin alpha4 subunit at a functional level did not occur in mi/mi CMCs. In the promoter region of the alpha4 subunit gene, there was a CACTTG motif to which normal MITF (+- MITF) bound. The coexpression of +-MITF but not of mi-MITF transactivated the promoter of the alpha4 subunit gene. The deletion or mutation of the CACTTG motif abolished the transactivation by +-MITF, suggesting that +-MITF directly transactivated the gene encoding alpha4 subunit of integrin.
Kim
D K
DK
Department of Pathology, the Department of Internal Medicine II, the Department of Hematology and Oncology, Osaka University Medical School, Suita, Japan.
Morii
E
E
Ogihara
H
H
Hashimoto
K
K
Oritani
K
K
Lee
Y M
YM
Jippo
T
T
Adachi
S
S
Kanakura
Y
Y
Kitamura
Y
Y
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D018257:Helix-Loop-Helix Motifs / Q000502:physiology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D016350:Leucine Zippers / Q000502:physiology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051739:Microphthalmia-Associated Transcription Factor; D009154:Mutation / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000187:drug effects
D004268:DNA-Binding Proteins; D039041:Integrin alpha4beta1; D016023:Integrins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D016201:Receptors, Lymphocyte Homing; D014157:Transcription Factors