Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells

Richard H. Scheuermann, Emilian Racila, Thomas Tucker, Eitan Yefenof, Nancy E. Street, Ellen S. Vitetta, Louis Picker, Jonathan W. Uhr

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4048-4052
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number9
StatePublished - Apr 26 1994
Externally publishedYes

Fingerprint

B-Cell Lymphoma
Cell Cycle Checkpoints
Protein-Tyrosine Kinases
Apoptosis
Immunoglobulins
Membranes
SCID Mice
Burkitt Lymphoma
Antisense Oligonucleotides
Ligation
Anti-Idiotypic Antibodies
Signal Transduction
Lymphoma
B-Lymphocytes
Cell Line
Antibodies
Growth
Neoplasms

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Scheuermann, R. H., Racila, E., Tucker, T., Yefenof, E., Street, N. E., Vitetta, E. S., ... Uhr, J. W. (1994). Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells. Proceedings of the National Academy of Sciences of the United States of America, 91(9), 4048-4052.

Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells. / Scheuermann, Richard H.; Racila, Emilian; Tucker, Thomas; Yefenof, Eitan; Street, Nancy E.; Vitetta, Ellen S.; Picker, Louis; Uhr, Jonathan W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 9, 26.04.1994, p. 4048-4052.

Research output: Contribution to journalArticle

Scheuermann, RH, Racila, E, Tucker, T, Yefenof, E, Street, NE, Vitetta, ES, Picker, L & Uhr, JW 1994, 'Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 9, pp. 4048-4052.
Scheuermann, Richard H. ; Racila, Emilian ; Tucker, Thomas ; Yefenof, Eitan ; Street, Nancy E. ; Vitetta, Ellen S. ; Picker, Louis ; Uhr, Jonathan W. / Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 9. pp. 4048-4052.
@article{bcd50d7974034d8abe9c4ab273d22668,
title = "Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells",
abstract = "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.",
author = "Scheuermann, {Richard H.} and Emilian Racila and Thomas Tucker and Eitan Yefenof and Street, {Nancy E.} and Vitetta, {Ellen S.} and Louis Picker and Uhr, {Jonathan W.}",
year = "1994",
month = "4",
day = "26",
language = "English (US)",
volume = "91",
pages = "4048--4052",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "9",

}

TY - JOUR

T1 - Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells

AU - Scheuermann, Richard H.

AU - Racila, Emilian

AU - Tucker, Thomas

AU - Yefenof, Eitan

AU - Street, Nancy E.

AU - Vitetta, Ellen S.

AU - Picker, Louis

AU - Uhr, Jonathan W.

PY - 1994/4/26

Y1 - 1994/4/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028216331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028216331&partnerID=8YFLogxK

M3 - Article

VL - 91

SP - 4048

EP - 4052

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 9

ER -