Abstract
Signaling molecules such as p21ras (Ras), mitogen-activated protein kinase (MAPK), and Akt kinase play pivotal roles in the proliferation and survival of lymphoid cells in response to many kinds of stimulation. It is not fully understood, however, how these molecules participate in the growth of malignant lymphoid cells.We determined whether Ras, MAPKs such as extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 MAPK, and Akt kinase are activated in B-cell tumors, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, Burkitt-like lymphoma, diffuse large B-cell lymphoma, and plasma cell leukemia.We found that Lyn protein tyrosine kinase was constitutively phosphorylated on tyrosine, and that ERK and p38 MAPK were constitutively active in all cases of the B-cell tumor. In contrast, activation of Ras and Akt kinase was found in limited cases, and JNK kinase activity was not observed in any case. These results suggest that ERK and p38 play roles in the oncogenesis of B-cell tumors.
Similar content being viewed by others
References
Chang L, Karin M. Mammalian MAP kinase signalling cascades.Nature. 2001;410:37–40.
O’Gorman DM, Cotter TG. Molecular signals in anti-apoptotic survival pathways.Leukemia. 2001;15:21–34.
Nagata Y, Takahashi N, Davis RJ, Todokoro K. Activation of p38 MAP kinase and JNK but not ERK is required for erythropoietininduced erythroid differentiation.Blood. 1998;92:1859–1869.
Jacobs-Helber SM, Ryan JJ, Sawyer S. JNK and p38 are activated by erythropoietin (EPO) but are not induced in apoptosis following EPO withdrawal in EPO-dependent HCD57 cells.Blood. 2000;96:933–940.
Yamaguchi H, Wang H-G. The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change.Oncogene. 2001;20:7779–7786.
Hoshino R, Chatani Y, Yamori T, et al. Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors.Oncogene. 1999;18:813–822.
Kawauchi K, Ogasawara T, Yasuyama M. Activation of extracellular signal-regulated kinase through B-cell antigen receptor in B-cell chronic lymphocytic leukemia.Int J Hematol. 2002;75:508–513.
Reuter CWM, Morgan MA, Bergmann L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies?Blood. 2000;96:1655–1669.
Whalen AM, Galasinski SC, Shapiro PS, Nahreini TS, Ahn NG. Megakaryocytic differentiation induced by constitutive activation of mitogen-activated protein kinase kinase.Mol Cell Biol. 1997;17:1947–1958.
Kurosaki T. Genetic analysis of B cell antigen receptor signaling.Annu Rev Immunol. 1999;17:555–592.
Turner M., Schweighoffer E, Colucci F, Di Santo JP, Tybulewicz L. Tyrosine kinase SYK: essential functions for immunoreceptor signalling.Immunol Today. 2000;21:148–154.
Hsueh RC, Scheuermann RH. Tyrosine kinase activation in the decision between growth, differentiation, and death responses initiated from the B cell antigen receptor.Adv Immunol. 2000;75:283–310.
Wilkinson MG, Millar JB. Control of the eukaryotic cell cycle by MAP kinase signaling pathways.FASEB J. 2000;14:2147–2157.
Srinivasa SP, Doshi PD. Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways cooperate in mediating cytokine-induced proliferation of a leukemic cell line.Leukemia. 2002;16:244–253.
Korus M, Mahon GM, Cheng L, Whitehead IP. p38 MAPK mediated activation of NK-κB by the RhoGEF domain of Bcr.Oncogene. 2002;21:4601–4612.
Recio JA, Merlino G. Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells through p38 MAPK, ATF-2 and cyclin D1.Oncogene. 2002;21:1000–1008.
Andjelic S, Hsia C, Suzuki H, Kadowaki T, Koyasu S, Liou H-C. Phosphatidylinositol 3-kinase and NF-κB/Rel are at the divergence of CD40-mediated proliferation and survival pathways.J Immunol. 2000;165:3860–3867.
Tu Y, Gardner A, Lichtenstein A. The phosphatidylinositol 3-kinase/ AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses.Cancer Res. 2000;60:6763–6770.
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article is available at http://dx.doi.org/10.1007/BF03191330.
About this article
Cite this article
Ogasawara, T., Yasuyama, M. & Kawauchi, K. Constitutive Activation of Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase in B-Cell Lymphoproliferative Disorders. Int J Hematol 77, 364–370 (2003). https://doi.org/10.1007/BF02982645
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02982645