Basu A, You S A, Haldar S
Rammelkamp Center for Education, Department of Pharmacology, Ireland Cancer Center, MetroHealth, Case Western Reserve University, Cleveland, OH 44109-1998, USA.
Int J Oncol. 2000 Mar;16(3):497-500. doi: 10.3892/ijo.16.3.497.
The anticancer drugs affecting either microtubule polymerization or depolymerization could trigger Bcl2 phosphorylation in mitotic phase of the cell cycle. By systematic site directed mutagenesis studies, we have previously mapped taxol induced phosphorylation sites to be Ser-70 and 87 residues of Bcl2 protein. Interestingly, sequences surrounding both serine-70 and serine-87 residues represent MAP kinase consensus motif. Since Bcl2 phosphorylation predominantly occurs at site consensus to MAP kinase family members, we were interested to test whether Erk2 or Jun kinase is involved in this pathway. Our in vitro studies document that stress activated kinase, JNK1 is responsible for Bcl2 phosphorylation.
影响微管聚合或解聚的抗癌药物可在细胞周期的有丝分裂期触发Bcl2磷酸化。通过系统的定点诱变研究，我们之前已将紫杉醇诱导的磷酸化位点定位到Bcl2蛋白的Ser-70和87残基。有趣的是，丝氨酸-70和丝氨酸-87残基周围的序列代表丝裂原活化蛋白激酶（MAP激酶）共有基序。由于Bcl2磷酸化主要发生在与MAP激酶家族成员一致的位点，我们有兴趣测试细胞外信号调节激酶2（Erk2）或Jun激酶是否参与此途径。我们的体外研究表明，应激激活激酶JNK1负责Bcl2磷酸化。
