Activation of extracellular signal-regulated kinase through B-cell antigen receptor in B-cell chronic lymphocytic...

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.