Heyninck K, Beyaert R
Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent University, Technologiepark, B-9052, Gent, Belgium.
Oncogene. 2006 Mar 16;25(12):1693-5. doi: 10.1038/sj.onc.1209157.
Protein kinases are critically involved in signaling pathways that regulate cell growth, differentiation, activation, and survival. Lck, a member of the Src family of protein tyrosine kinases, plays a key role in T-lymphocyte activation and differentiation. However, under certain conditions Lck is also involved in the induction of apoptosis. In this issue of Oncogene, Samraj et al. used the Lck-defective JCaM1.6 cell line to demonstrate the critical role of Lck in the apoptotic response of T-cell leukemia cells to several chemotherapeutic drugs. They further showed that Lck controls the mitochondrial death pathway by regulating proapoptotic Bak expression. This chemosensitizing effect of Lck is independent of T-cell receptor signaling and does not require the kinase activity of Lck. These findings demonstrate that Lck might be part of two independent signaling pathways leading to either cell proliferation or apoptosis, and reveal a hitherto unrecognized link between Lck, Bak, and chemosensitivity of human leukemic cells.
蛋白激酶在调节细胞生长、分化、激活和存活的信号通路中起着关键作用。Lck是蛋白酪氨酸激酶Src家族的成员之一，在T淋巴细胞的激活和分化中起关键作用。然而，在某些条件下，Lck也参与凋亡的诱导。在本期《癌基因》杂志中，Samraj等人使用Lck缺陷的JCaM1.6细胞系来证明Lck在T细胞白血病细胞对几种化疗药物的凋亡反应中的关键作用。他们进一步表明，Lck通过调节促凋亡蛋白Bak的表达来控制线粒体死亡途径。Lck的这种化学增敏作用独立于T细胞受体信号传导，且不需要Lck的激酶活性。这些发现表明，Lck可能是导致细胞增殖或凋亡的两条独立信号通路的一部分，并揭示了Lck、Bak与人类白血病细胞化学敏感性之间迄今未被认识的联系。
