Activation of extracellular signal-regulated kinase through B-cell antigen receptor in B-cell chronic lymphocytic leukemia.
B-cell chronic lymphocytic leukemia (B-CLL) cells express on their surface membranes immunoglobulin (Ig) M or IgD, both of which normally function as B-cell antigen receptors (BCRs). However, in contrast to normal B-cells, in B-CLL cells several important signaling pathways, such as the activation of protein tyrosine kinase via BCR, are defective. We have examined whether the activities of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38 MAPK, and Akt kinase, are functional in B-CLL cells, because these kinases play critical roles in activation in response to BCR stimulation, tumor cell growth, and survival. In B-CLL cells, BCR cross-linking neither induced activation nor enhanced the activities of Lyn, Syk, p21ras, JNK, p38 MAPK, or Akt kinases, whereas p38 MAPK and Akt were constitutively active. In contrast, BCR cross-linking resulted in ERK activation, although the activation in quiescent cells was case dependent. These results suggest that some signaling pathways, such as the activation of ERK through BCR, are functional in B-CLL cells despite the extensive impairment of signaling pathways.
Kawauchi
Kiyotaka
K
Department of Medicine, Tokyo Women's Medical University Daini Hospital, Japan. ochamegm@dnh.twmu.ac.jp
Ogasawara
Toshie
T
Yasuyama
Masako
M
D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000502:physiology; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000072377:Syk Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases / Q000502:physiology
D004792:Enzyme Precursors; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; 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; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)