Watts J D, Welham M J, Kalt L, Schrader J W, Aebersold R
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
J Immunol. 1993 Dec 15;151(12):6862-71.
p56lck, a member of the src family of non-receptor protein tyrosine kinases, is expressed almost exclusively in cells of lymphoid origin. p56lck is known to associate with the T lymphocyte surface glycoproteins CD4 and CD8, and plays a critical role in both T lymphocyte development and activation. p56lck also associates with the beta-subunit of the IL-2R, and is activated when IL-2 binds to its receptor. Using primary cultures of Con A-activated normal splenic mouse T lymphocytes, we observed an IL-2-induced sequence of events involving p56lck. We saw a rapid (within 1 to 2 min) and transient increase in p56lck kinase activity, which preceded the activation of both the p42erk-2 and p44erk-1 mitogen-activated protein kinases, maximal activation of which was observed after 10 min. We also observed an IL-2-induced shift in the electrophoretic mobility of p56lck from an apparent molecular mass of 56 kDa (p56lck) to 60 kDa (p60lck), which reached a maximum at 15 min, the level of p60lck remaining constant for up to 4 h thereafter. This IL-2-induced shift correlated with the phosphorylation of serine-59 of p56lck, a site that mitogen-activated protein kinases are capable of modifying in vitro. The implications of these results for the understanding of both p56lck function and lymphoid cell receptor signaling pathways are discussed.
p56lck是非受体蛋白酪氨酸激酶src家族的成员之一，几乎只在淋巴起源的细胞中表达。已知p56lck与T淋巴细胞表面糖蛋白CD4和CD8相关联，并且在T淋巴细胞的发育和激活过程中发挥关键作用。p56lck还与IL-2R的β亚基相关联，当IL-2与其受体结合时被激活。利用伴刀豆球蛋白A激活的正常脾脏小鼠T淋巴细胞的原代培养物，我们观察到了一系列由IL-2诱导的涉及p56lck的事件。我们看到p56lck激酶活性迅速（在1至2分钟内）且短暂增加，这先于p42erk-2和p44erk-1丝裂原活化蛋白激酶的激活，10分钟后观察到它们的最大激活。我们还观察到IL-2诱导p56lck的电泳迁移率从表观分子量56 kDa（p56lck）转变为60 kDa（p60lck），在15分钟时达到最大值，此后p60lck的水平在长达4小时内保持恒定。这种由IL-2诱导的转变与p56lck丝氨酸-59的磷酸化相关，丝裂原活化蛋白激酶在体外能够修饰该位点。讨论了这些结果对于理解p56lck功能和淋巴细胞受体信号通路的意义。
