Melamed I, Patel H, Brodie C, Gelfand E W
Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado, 80206, USA.
Cell Immunol. 1999 Feb 1;191(2):83-9. doi: 10.1006/cimm.1998.1402.
Engagement of the B-cell antigen receptor (BCR) or the nerve growth factor receptor (NGFR/TrkA) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. We show that addition of NGF or anti-IgM antibody leads to the early tyrosine phosphorylation of p95(vav), which is expressed exclusively in hematopoietic cells; NGF, similar to crosslinking the BCR, also results in the rapid activation of Ras. The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase, whereas signaling through the BCR uses a different tyrosine kinase. We also show that NGF induces tyrosine phosphorylation of Shc and its association with Grb2. Vav and Ras with the adaptor proteins Shc and Grb2 appear to serve as a link between different receptor-mediated signaling pathways and, in human B cells, may play an important regulatory role in neuroimmune interactions.
B细胞抗原受体（BCR）或神经生长因子受体（NGFR/TrkA）的激活会诱导多种酪氨酸激酶活化，导致众多细胞内底物磷酸化。我们发现，添加神经生长因子（NGF）或抗IgM抗体可导致仅在造血细胞中表达的p95(vav)发生早期酪氨酸磷酸化；与BCR交联类似，NGF也会导致Ras迅速活化。NGF引发的Vav磷酸化和Ras活化是通过Trk酪氨酸激酶介导的，而通过BCR的信号传导则使用不同的酪氨酸激酶。我们还发现，NGF可诱导Shc酪氨酸磷酸化及其与Grb2的结合。Vav和Ras与衔接蛋白Shc和Grb2似乎在不同受体介导的信号通路之间起连接作用，并且在人类B细胞中，可能在神经免疫相互作用中发挥重要的调节作用。
