Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells.
Signal transduction initiated by binding of antibodies to cell surface molecules can have an important impact on the growth of tumor cells. The malignant behavior of the murine lymphoma BCL1 can be suppressed and the neoplastic cells can be induced to enter a dormant state by in vivo ligation of membrane immunoglobulin. Anti-CD19 antibodies can prolong the survival of SCID mice challenged with the human Burkitt lymphoma cell line, Daudi. Here, we show that cross-linking of membrane immunoglobulin on both murine BCL1 and human Daudi cells initiates a cascade of signals leading to the induction of both apoptosis and cell cycle arrest in vitro. Using antisense oligonucleotides, we demonstrate that the immunoglobulin-associated Lyn tyrosine kinase is required for anti-immunoglobulin-mediated cell cycle arrest but is not required for the signal leading to apoptosis. These results define a branch point in the cytosolic signaling pathways mediating cell cycle arrest and apoptosis. In Daudi cells, Lyn is also critical for cell cycle arrest induced by anti-CD19 signaling. Thus, the Lyn tyrosine kinase may be an important mediator of cell cycle arrest in neoplastic B lymphocytes and, perhaps, other cell types.
Scheuermann
R H
RH
Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas 75235.
Racila
E
E
Tucker
T
T
Yefenof
E
E
Street
N E
NE
Vitetta
E S
ES
Picker
L J
LJ
Uhr
J W
JW
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D006801:Humans; D066298:In Vitro Techniques; D016393:Lymphoma, B-Cell / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D016376:Oligonucleotides, Antisense; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases