CDK5 对 PBK 的 Thr9 位磷酸化与泌乳素瘤的侵袭相关。
Phosphorylation of PBK at Thr9 by CDK5 correlates with invasion of prolactinomas.
机构信息
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
出版信息
CNS Neurosci Ther. 2024 Feb;30(2):e14629. doi: 10.1111/cns.14629.
CONTEXT
Prolactinomas are the most prevalent functional pituitary neuroendocrine tumors (PitNETs), and they are invasive to surrounding anatomic structures. The detailed mechanisms of invasion are not yet clear.
OBJECTIVE
We explored the role of PBK phosphorylation in the proliferation and invasion of prolactinomas and its possible mechanism.
RESULTS
We report that PBK directly binds to and is phosphorylated at Thr9 by cyclin-dependent kinase 5 (CDK5), which promotes GH3 cell EMT progression and proliferation. Phosphorylation of PBK at Thr9 (pPBK-T9) by CDK5 enhances the stability of PBK. p38 is one of the downstream targets of PBK, and its phosphorylation is reduced as pPBK-T9 increases in vivo and in vitro. Furthermore, we found that pPBK-T9 is highly expressed in invasive PitNETs and was significantly correlated with invasion by univariate and multivariate analyses.
CONCLUSIONS
Phosphorylation of PBK at Thr9 by CDK5 promotes cell proliferation and EMT progression in prolactinomas.
背景
催乳素瘤是最常见的功能性垂体神经内分泌肿瘤（PitNETs），它们会侵袭周围的解剖结构。侵袭的详细机制尚不清楚。
目的
我们探讨了 PBK 磷酸化在催乳素瘤增殖和侵袭中的作用及其可能的机制。
结果
我们报告 PBK 可直接与周期蛋白依赖性激酶 5（CDK5）结合，并在 Thr9 处被 CDK5 磷酸化，这促进了 GH3 细胞 EMT 进程和增殖。CDK5 磷酸化 PBK 第 9 位苏氨酸（pPBK-T9）可增强 PBK 的稳定性。p38 是 PBK 的下游靶点之一，其在体内和体外随着 pPBK-T9 的增加而减少。此外，我们发现 pPBK-T9 在侵袭性 PitNETs 中高度表达，并且在单变量和多变量分析中与侵袭性显著相关。
结论
CDK5 磷酸化 PBK 第 9 位苏氨酸可促进催乳素瘤中的细胞增殖和 EMT 进程。
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