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-S rc. 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 Spl were identified in the promoter region of the c-src gene. Surprisingly, Spl and Spl mRNA we re not found in monocytes that were freshly isolated or incubated with cont rol antibody. Stimulation with anti-CD98HC mAb also resulted in the express ion of Spl and its translocation to the nucleus. Herbimycin A, genistein, m anumycin A, PD-98059, SB203580, and HBJ127 suppressed CD98HC-mediated c-src and Spl mRNA induction. On the contrary, H-7, Wortmannin, HA1077, and Y-27 632 showed no effect on c-Src and Spl induction. Furthermore, anti-CD98HC m Ab induced activation of tyrosine kinases and ERK kinases. These findings s uggest that the tyrosine kinase(s)-Ras-MAPK-Sp1 pathway(s) is involved in C D98HC-mediated induction. of c-Src in human blood monocytes, (C) 2000 Acade mic Press.