Integrin-associated protein/CD47 regulates motile activity in human B-cell lines through CDC42.
Cell migration requires a dynamic interaction between the cell, its substrate, and the cytoskeleton-associated motile apparatus. Integrin-associated protein (IAP)/CD47 is a 50-kd cell surface protein that is physically associated with beta3 integrins and that modulates the functions of beta3 integrins in various cells. However, in B-lymphocytes that express beta1 integrins but few beta3 integrins, the roles of IAP/CD47 remain to be determined. Cross-linking of IAP/CD47 by the immobilized anti-IAP/CD47 monoclonal antibody (mAb) B6H12, but not 2D3, produced signals to promote polarization with lamellipodia, a characteristic morphology during leukocyte migration, in pre-B and mature B-cell lines (BALL, Nalm6, ONHL-1, Daudi), but not in myeloma cell lines (RPMI8226, OPM-2). In the presence of the immobilized fibronectin (FN), soluble B6H12 could increase the rate of the polarization and activate migratory activity of BALL cells to FN in a transwell filter assay. Furthermore, the dominant-negative form of CDC42 completely blocked B6H12-induced morphologic and functional changes without inhibiting phorbol 12-myristate 13-acetate-induced spreading on FN in BALL cells, whereas the dominant-negative form of Rac1 inhibited all these changes. These findings demonstrate that in B-lymphocytes, IAP/CD47 may transduce the signals to activate the migratory activity, in which CDC42 may be specifically involved, and that IAP/CD47 shows synergistic effect with alpha4beta1 on B-cell migration. These findings would provide new insight into the role of IAP/CD47 on B-cell function.
Yoshida
H
H
Department of Internal Medicine and Molecular Science and the Department of Hematology and Oncology, Osaka University, Suita, Japan.
Tomiyama
Y
Y
Ishikawa
J
J
Oritani
K
K
Matsumura
I
I
Shiraga
M
M
Yokota
T
T
Okajima
Y
Y
Ogawa
M
M
Miyagawa
J i
Ji
Nishiura
T
T
Matsuzawa
Y
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002051:Burkitt Lymphoma; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000502:physiology*; D016764:Cell Polarity; D003432:Cross-Linking Reagents; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D017469:Receptors, Fibronectin / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D005353:Fibronectins; D019012:Integrin beta1; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins; D020764:cdc42 GTP-Binding Protein