Phosphorylation of PBK at Thr9 by CDK5 correlates with invasion of prolactinomas.

Qiuyue Fang, Changxiaofeng Liu, Ding Nie, Jing Guo, Weiyan Xie, Yazhuo Zhang

CNS neuroscience & therapeutics 2024 Feb

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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. We explored the role of PBK phosphorylation in the proliferation and invasion of prolactinomas and its possible mechanism. 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. Phosphorylation of PBK at Thr9 by CDK5 promotes cell proliferation and EMT progression in prolactinomas. © 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Citation

Qiuyue Fang, Changxiaofeng Liu, Ding Nie, Jing Guo, Weiyan Xie, Yazhuo Zhang. Phosphorylation of PBK at Thr9 by CDK5 correlates with invasion of prolactinomas. CNS neuroscience & therapeutics. 2024 Feb;30(2):e14629