抗CD98/FRP-1单克隆抗体以依赖Sp1的方式诱导人血单核细胞中c-Src的表达。

Induction of c-Src in human blood monocytes by anti-CD98/FRP-1 mAb in an Sp1-dependent fashion.

作者信息

Miyamoto N, Higuchi Y, Tsurudome M, Ito M, Nishio M, Kawano M, Sudo A, Kato K, Uchida A, Ito Y

机构信息

Department of Microbiology, Department of Orthopedics, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514-8507, Japan.

出版信息

Cell Immunol. 2000 Sep 15;204(2):105-13. doi: 10.1006/cimm.2000.1696.

DOI:10.1006/cimm.2000.1696

PMID:11069718

Abstract

Freshly isolated human blood monocytes expressed neither c-src mRNA nor c-Src. However, when monocytes were incubated with anti-CD98 heavy chain (HC) mAb, expression of c-src mRNA, c-Src, and activated c-Src was induced. Many binding sites for the ubiquitous transcription factor Sp1 were identified in the promoter region of the c-src gene. Surprisingly, Sp1 and Sp1 mRNA were not found in monocytes that were freshly isolated or incubated with control antibody. Stimulation with anti-CD98HC mAb also resulted in the expression of Sp1 and its translocation to the nucleus. Herbimycin A, genistein, manumycin A, PD-98059, SB203580, and HBJ127 suppressed CD98HC-mediated c-src and Sp1 mRNA induction. On the contrary, H-7, Wortmannin, HA1077, and Y-27632 showed no effect on c-Src and Sp1 induction. Furthermore, anti-CD98HC mAb induced activation of tyrosine kinases and ERK kinases. These findings suggest that the tyrosine kinase(s)-Ras-MAPK-Sp1 pathway(s) is involved in CD98HC-mediated induction of c-Src in human blood monocytes.

摘要

新鲜分离的人血单核细胞既不表达c-src mRNA也不表达c-Src。然而，当单核细胞与抗CD98重链（HC）单克隆抗体孵育时，c-src mRNA、c-Src和活化的c-Src的表达被诱导。在c-src基因的启动子区域鉴定出许多普遍存在的转录因子Sp1的结合位点。令人惊讶的是，在新鲜分离的或与对照抗体孵育的单核细胞中未发现Sp1和Sp1 mRNA。用抗CD98HC单克隆抗体刺激也导致Sp1的表达及其向细胞核的转位。赫伯霉素A、染料木黄酮、马努霉素A、PD-98059、SB203580和HBJ127抑制CD98HC介导的c-src和Sp1 mRNA诱导。相反，H-7、渥曼青霉素、HA1077和Y-27632对c-Src和Sp1诱导没有影响。此外，抗CD98HC单克隆抗体诱导酪氨酸激酶和ERK激酶的活化。这些发现表明酪氨酸激酶-Ras-MAPK-Sp1途径参与了人血单核细胞中CD98HC介导的c-Src诱导。