Minami Y, Kono T, Yamada K, Kobayashi N, Kawahara A, Perlmutter R M, Taniguchi T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
EMBO J. 1993 Feb;12(2):759-68. doi: 10.1002/j.1460-2075.1993.tb05710.x.
Previous studies demonstrate that p56lck, a member of the src-family of protein tyrosine kinases (PTKs), can physically associate with the interleukin-2 (IL-2) receptor beta chain (IL-2R beta) and that IL-2 receptor engagement stimulates p56lck activity. To examine the mechanisms underlying p56lck PTK activation by IL-2, we established a mouse pro-B cell line, BAF-B03, expressing both IL-2R beta (either the wild-type or mutant forms) and mouse p56lck at high levels. BAF-B03 cells expressing a mutant IL-2R beta chain lacking an 'acidic' region of the cytoplasmic domain, previously shown to be essential for association with p56lck, fail to induce p56lck PTK activation upon IL-2 stimulation. This suggests that the association of p56lck with the IL-2R beta chain, despite its low stoichiometry, is required for the activation of cellular p56lck PTK upon IL-2 stimulation. Intriguingly, BAF-B03 cells expressing an IL-2R beta chain which lacks a different cytoplasmic region, the 'serine-rich' region, also fail to activate p56lck in response to IL-2. Hence, physical association of p56lck with the IL-2R beta chain is not by itself sufficient to permit IL-2-mediated regulation of this PTK. Additional experiments suggest that one result of PTK activation is the accumulation of c-fos and c-jun transcripts.
先前的研究表明，蛋白酪氨酸激酶（PTK）src家族成员p56lck可与白细胞介素-2（IL-2）受体β链（IL-2Rβ）发生物理性结合，且IL-2受体的结合可刺激p56lck活性。为研究IL-2激活p56lck PTK的机制，我们建立了一种小鼠前B细胞系BAF-B03，该细胞系高水平表达IL-2Rβ（野生型或突变型）和小鼠p56lck。表达缺乏细胞质结构域“酸性”区域的突变型IL-2Rβ链的BAF-B03细胞，先前已证明该区域对于与p56lck结合至关重要，在IL-2刺激下无法诱导p56lck PTK激活。这表明，尽管p56lck与IL-2Rβ链的化学计量比很低，但在IL-2刺激下激活细胞p56lck PTK需要二者结合。有趣的是，表达缺乏另一个细胞质区域即“富含丝氨酸”区域的IL-2Rβ链的BAF-B03细胞，对IL-2刺激也无法激活p56lck。因此，p56lck与IL-2Rβ链的物理性结合本身不足以实现IL-2介导的对该PTK的调控。进一步的实验表明，PTK激活的一个结果是c-fos和c-jun转录本的积累。
