MARK1

Last update 08 May 2025

Basic Info

Synonyms

KIAA1477, MAP/microtubule affinity-regulating kinase 1, MARK

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Introduction

Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3).

100 Clinical Results associated with MARK1

100 Translational Medicine associated with MARK1

0 Patents (Medical) associated with MARK1

Literatures (Medical) associated with MARK1

07 Nov 2024·Open Medicine

MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE

Article

Author: Liu, Yubin ; Chen, Zhiyuan ; Zheng, Jianming ; Mi, Wenting ; Lu, Xin

AbstractPurposeThis study aimed to investigate the role of microtubule-affinity regulatory protein kinase 1 (MARK1) in hepatocellular carcinoma (HCC) progression, its association with sorafenib sensitivity, and the interplay between MARK1 and POTE Ankyrin domain family member E(POTEE) in HCC cells.MethodsQuantitative real-time polymerase chain reaction analysis was used to assess MARK1 and POTEE expression in 60 pairs of HCC tissues and cell lines. The correlation between MARK1 levels, clinicopathological features, and patient prognosis was analyzed. Sorafenib-resistant HCC cell models were developed, followed by MARK1 overexpression to evaluate its impact on cell functions. Luciferase reporter assays and rescue experiments were conducted to elucidate the MARK1–POTEE regulatory mechanism.ResultsMARK1 exhibited decreased mRNA expression in HCC tissues and cells, correlating with adverse clinicopathological features and poorer patient survival. Luciferase assays confirmed direct binding between MARK1 and POTEE. Sorafenib treatment increased MARK1 protein levels, reduced POTEE, and inhibited cell proliferation. Overexpressing MARK1 suppressed sorafenib-induced proliferation in resistant cells, while co-overexpression of MARK1 and POTEE reversed this effect.ConclusionMARK1 potentially restrains HCC progression and enhances sorafenib resistance by negatively modulating POTEE expression, highlighting its significance as a therapeutic target in HCC treatment.

01 Jul 2024·British Journal of Pharmacology

A novel role for microtubule affinity‐regulating kinases in neuropathic pain

Article

Author: Xu, Yang ; Yu, Lin-Yao ; Tian, Jing-Wei ; Su, Chun-Yu ; Wang, Zhe-Zhe ; Sun, Zhi-Hong ; Li, Chun-Mei ; Shi, Yao-Qin ; Zhang, Wei ; Gao, Yong-Lin ; Wang, Hong-Bo

AbstractBackground and PurposeNeuropathic pain affects millions of patients, but there are currently few viable therapeutic options available. Microtubule affinity‐regulating kinases (MARKs) regulate the dynamics of microtubules and participate in synaptic remodelling. It is unclear whether these changes are involved in the central sensitization of neuropathic pain. This study examined the role of MARK1 or MARK2 in regulating neurosynaptic plasticity induced by neuropathic pain.Experimental ApproachA rat spinal nerve ligation (SNL) model was established to induce neuropathic pain. The role of MARKs in nociceptive regulation was assessed by genetically knocking down MARK1 or MARK2 in amygdala and systemic administration of PCC0105003, a novel small molecule MARK inhibitor. Cognitive function, anxiety‐like behaviours and motor coordination capability were also examined in SNL rats. Synaptic remodelling‐associated signalling changes were detected with electrophysiological recording, Golgi‐Cox staining, western blotting and qRT‐PCR.Key ResultsMARK1 and MARK2 expression levels in amygdala and spinal dorsal horn were elevated in SNL rats. MARK1 or MARK2 knockdown in amygdala and PCC0105003 treatment partially attenuated pain‐like behaviours along with improving cognitive deficit, anxiogenic‐like behaviours and motor coordination in SNL rats. Inhibition of MARKs signalling reversed synaptic plasticity at the functional and structural levels by suppressing NR2B/GluR1 and EB3/Drebrin signalling pathways both in amygdala and spinal dorsal horn.Conclusion and ImplicationsThese results suggest that MARKs‐mediated synaptic remodelling plays a key role in the pathogenesis of neuropathic pain and that pharmacological inhibitors of MARKs such as PCC0105003 could represent a novel therapeutic strategy for the management of neuropathic pain.

01 Jun 2024·Experimental Neurology

MARK1 regulates dendritic spine morphogenesis and cognitive functions in vivo

Article

Author: Bhagwat, Maitreyee ; Dindigal, Ankitha H ; Shear, Rebecca ; Kelly-Castro, Emily C ; Zhang, Huaye

Dendritic spines play a pivotal role in synaptic communication and are crucial for learning and memory processes. Abnormalities in spine morphology and plasticity are observed in neurodevelopmental and neuropsychiatric disorders, yet the underlying signaling mechanisms remain poorly understood. The microtubule affinity regulating kinase 1 (MARK1) has been implicated in neurodevelopmental disorders, and the MARK1 gene shows accelerated evolution in the human lineage suggesting a role in cognition. However, the in vivo role of MARK1 in synaptogenesis and cognitive functions remains unknown. Here we show that forebrain-specific conditional knockout (cKO) of Mark1 in mice causes defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons with a significant reduction in spine density. In addition, we found loss of MARK1 causes synaptic accumulation of GKAP and GluA2. Furthermore, we found that MARK1 cKO mice show defects in spatial learning in the Morris water maze and reduced anxiety-like behaviors in the elevated plus maze. Taken together, our data show a novel role for MARK1 in regulating dendritic spine morphogenesis and cognitive functions in vivo.

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