Brunswick M, Samelson L E, Mond J J
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1311-4. doi: 10.1073/pnas.88.4.1311.
It has been found that the principal biochemical pathway activated in B cells stimulated by antigen- or anti-immunoglobulin-mediated crosslinking of surface immunoglobulin is that resulting in hydrolysis of phosphatidylinositol bisphosphate with generation of diacylglycerol and inositol trisphosphate. Recent evidence suggests that surface immunoglobulin-mediated B-cell activation can proceed without detectable increases in the concentration of either diacylglycerol or intracellular Ca2+ concentration, implicating involvement of other non-protein-kinase-C/Ca2(+)-dependent signal-transduction pathways. Therefore, we sought evidence for activation of a signaling pathway that is associated with growth regulation in other cell types--i.e., the protein-tyrosine kinases. We now show that crosslinking of membrane immunoglobulin by mitogenic antibodies leads to rapid tyrosine phosphorylation of several cellular substrates, consistent with the induction of a tyrosine kinase activity. This increase in tyrosine phosphorylation is weakly (if at all) stimulated by other B-cell mitogens, including phorbol esters and ionophores, and does not require the presence of detectable protein kinase C. Furthermore, inhibition of anti-immunoglobulin-stimulated phosphatidylinositol bisphosphate hydrolysis does not inhibit activation of this tyrosine kinase-dependent pathway. These findings suggest that occupancy of the membrane immunoglobulin receptor may induce multiple pathways of activation.
现已发现，在抗原或抗免疫球蛋白介导的表面免疫球蛋白交联刺激下，B细胞中被激活的主要生化途径是导致磷脂酰肌醇二磷酸水解并生成二酰基甘油和肌醇三磷酸的途径。最近的证据表明，表面免疫球蛋白介导的B细胞激活过程中，二酰基甘油浓度或细胞内Ca2+浓度可能并未出现可检测到的升高，这意味着其他非蛋白激酶C/Ca2(+)-依赖性信号转导途径也参与其中。因此，我们寻找了与其他细胞类型生长调节相关的信号通路——即蛋白酪氨酸激酶——被激活的证据。我们现在表明，促有丝分裂抗体使膜免疫球蛋白交联会导致几种细胞底物迅速发生酪氨酸磷酸化，这与酪氨酸激酶活性的诱导一致。酪氨酸磷酸化的这种增加受到其他B细胞促有丝分裂原（包括佛波酯和离子载体）的微弱刺激（如果有的话），并且不需要可检测到的蛋白激酶C的存在。此外，抑制抗免疫球蛋白刺激的磷脂酰肌醇二磷酸水解并不抑制这条酪氨酸激酶依赖性途径的激活。这些发现表明，膜免疫球蛋白受体的占据可能会诱导多种激活途径。
