SRPK、CLK 和 DYRK 激酶在干细胞、发育和人类发育障碍中的功能。

Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.

机构信息

The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, UK.

出版信息

FEBS Lett. 2023 Oct;597(19):2375-2415. doi: 10.1002/1873-3468.14723. Epub 2023 Sep 4.

Abstract

Human developmental disorders encompass a wide range of debilitating physical conditions and intellectual disabilities. Perturbation of protein kinase signalling underlies the development of some of these disorders. For example, disrupted SRPK signalling is associated with intellectual disabilities, and the gene dosage of DYRKs can dictate the pathology of disorders including Down's syndrome. Here, we review the emerging roles of the CMGC kinase families SRPK, CLK, DYRK, and sub-family HIPK during embryonic development and in developmental disorders. In particular, SRPK, CLK, and DYRK kinase families have key roles in developmental signalling and stem cell regulation, and can co-ordinate neuronal development and function. Genetic studies in model organisms reveal critical phenotypes including embryonic lethality, sterility, musculoskeletal errors, and most notably, altered neurological behaviours arising from defects of the neuroectoderm and altered neuronal signalling. Further unpicking the mechanisms of specific kinases using human stem cell models of neuronal differentiation and function will improve our understanding of human developmental disorders and may provide avenues for therapeutic strategies.

摘要

人类发育障碍包括多种使人衰弱的身体状况和智力残疾。蛋白激酶信号的紊乱是这些障碍发展的基础。例如,SRPK 信号的中断与智力残疾有关,DYRK 基因的剂量可以决定包括唐氏综合征在内的多种疾病的病理。在这里,我们综述了 CMGC 激酶家族 SRPK、CLK、DYRK 及其亚家族 HIPK 在胚胎发育和发育障碍中的新兴作用。特别是,SRPK、CLK 和 DYRK 激酶家族在发育信号和干细胞调控中发挥关键作用,并能协调神经元发育和功能。模式生物的遗传研究揭示了关键表型,包括胚胎致死、不育、肌肉骨骼错误,以及最显著的是,神经外胚层缺陷和神经元信号改变导致的改变的神经行为。使用人类神经细胞分化和功能的干细胞模型进一步剖析特定激酶的机制,将有助于我们理解人类发育障碍,并可能为治疗策略提供途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c5e/10952393/bc9cb4157887/FEB2-597-2375-g008.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索