Constitutive activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in B-cell lymphoproliferative disorders.
Signaling molecules such as p21(ras) (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.
Ogasawara
Toshie
T
Department of Medicine, Tokyo Women's Medical University, Daini Hospital, Tokyo, Japan.
Yasuyama
Masako
M
Kawauchi
Kiyotaka
K
D000368:Aged; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D015448:Leukemia, B-Cell / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D011518:Proto-Oncogene Proteins; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins