Induction of c-Src in human blood monocytes by anti-CD98/FRP-1 mAb in an Sp1-dependent fashion.
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.
Miyamoto
N
N
Department of Microbiology, Department of Orthopedics, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514-8507, Japan. ito@doc.medic.mie-u.ac
Higuchi
Y
Y
Tsurudome
M
M
Ito
M
M
Nishio
M
M
Kawano
M
M
Sudo
A
A
Kato
K
K
Uchida
A
A
Ito
Y
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D027261:Fusion Regulatory Protein-1; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D047428:Protein Kinase Inhibitors; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D019061:src-Family Kinases / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; C054474:manumycin