Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, via Alcide de Gasperi 2, I-53100 Siena, Italy.
Med Res Rev. 2012 Sep;32(5):968-98. doi: 10.1002/med.20230. Epub 2011 Jan 16.
The LIM kinases 1 and 2 (LIMK1 and LIMK2) are dual specificity (serine/threonine and tyrosine) kinases. Although they show significant structural similarity, LIMK1 and LIMK2 show different expression, subcellular localization, and functions. They are involved in many cellular functions, such as migration, cycle, and neuronal differentiation and also have a role in pathological processes, such as cancer cell invasion and metastatis, as well as in neurodevelopmental disorders (namely, the William's syndrome). LIM kinases have a relevant number of known partners that are able to induce or limit the ability of LIMK1 and LIMK2 to phosphorylate and inactivate their major substrate, cofilin. On the contrary, only a limited number of small molecules that interact with the two proteins to modulate their kinase activity have been identified. In this review, the most important partners of LIM kinases and their modulating activity toward LIMKs are described. The small compounds identified as LIMK1 and LIMK2 modulators are also reported, as well as their role as possible therapeutic agents for LIMK-induced diseases.
LIM 激酶 1 和 2（LIMK1 和 LIMK2）是双特异性（丝氨酸/苏氨酸和酪氨酸）激酶。尽管它们表现出显著的结构相似性，但 LIMK1 和 LIMK2 表现出不同的表达、亚细胞定位和功能。它们参与许多细胞功能，如迁移、周期和神经元分化，并且在病理过程中也有作用，如癌细胞侵袭和转移，以及神经发育障碍（即威廉姆斯综合征）。LIM 激酶有许多已知的伴侣，这些伴侣能够诱导或限制 LIMK1 和 LIMK2 磷酸化并使其主要底物丝切蛋白失活的能力。相反，只有少数能够与这两种蛋白质相互作用来调节其激酶活性的小分子被鉴定出来。在这篇综述中，描述了 LIM 激酶的最重要的伴侣及其对 LIMKs 的调节活性。还报告了被鉴定为 LIMK1 和 LIMK2 调节剂的小分子化合物，以及它们作为 LIMK 诱导疾病的潜在治疗剂的作用。
