Fibronectin promotes cell proliferation of human pre-B cell line via its interactions with VLA-4 and VLA-5.
Fibronectin (FN) is thought to play an important role in various aspects of hematopoiesis through binding to very late antigen (VLA)-4 and VLA-5. Little is known, however, about the effects of FN on the proliferation of B cell progenitors. In this study, we investigated the effects of immobilized FN on the proliferation of the pre-B cell line, Nalm-6, which expresses both VLA-4 and VLA-5. Immobilized FN significantly promoted the proliferation of Nalm-6 cells through the synergistic effects of VLA-4 and VLA-5. Furthermore, FN induced the phosphorylation of mitogen-activated protein kinases (MAPKs) of Nalm-6 cells. The MAPK kinase 1 (MEK1) inhibitor, PD98059, and Src family tyrosine kinase inhibitor, herbimycin A, inhibited the FN-promoted proliferation of Nalm-6 cells. These results demonstrate that the interactions of FN and VLA-4/VLA-5 transmit the growth signals that are mediated through Src family tyrosine kinases and the MAPK cascade in Nalm-6 cells. The precise mechanism of synergistic effect of VLA-4 and VLA-5 on FN-promoted proliferation of Nalm-6 cells should be further investigated.
Harima
Akane
A
Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 2, Japan.
Nakaseko
Chiaki
C
Yokota
Akira
A
Kitagawa
Motoo
M
Morimoto
Chikao
C
Harigaya
Kenichi
K
Saito
Yasushi
Y
D016227:Benzoquinones / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D015448:Leukemia, B-Cell; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D005353:Fibronectins; D005419:Flavonoids; D039041:Integrin alpha4beta1; D039081:Integrin alpha5beta1; D047029:Lactams, Macrocyclic; D017828:Rifabutin; C020754:herbimycin; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one