Rho-associated coiled-coil kinase (ROCK) signaling and disease

Schofield, Alice; Bernard, Ora

doi:10.3109/10409238.2013.786671

Cited by 165 publications

(165 citation statements)

References 247 publications

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“…Since inhibition of RhoA and Rho kinase down-regulated cPLA 2 activation, we then asked whether Rho kinase had the same distribution as cPLA 2 and whether it could directly interact with cPLA 2 . We stained spinal cord neurons with Rho kinase (ROCK 1 or ROCK 2 ) and cPLA 2 antibodies and immunofluorescent secondary antibodies.…”

Section: Rock 1 and Rock 2 Two Isoforms Of Rho Kinase Co-localizedmentioning

confidence: 99%

“…TNF-α and glutamate induced activation of both RhoA/Rho kinase and cPLA 2 To dissect out the mechanism of neurotoxicity induced by TNF-α and glutamate, we examined RhoA/Rho kinase and cPLA 2 activities. The data showed that, following TNF-α and glutamate treatment, the active form of RhoA (RhoA-GTP), which was precipitated by Rhotekin beads, was increased significantly at 5 minutes (Fig.…”

Section: Combined Insults Of Tnf-α and Glutamate Induced Neurotoxicitmentioning

confidence: 99%

“…Briefly, spinal cord neurons on coverslips on day 7 were fixed by 4%PFA followed by washing with 0.01M PBS, blocking 1 hour with 5% goat serum-0.3% Triton X-100-PBS, and staining with anti-rabbit βIII tubulin(1:1000, Cell Signaling, USA), anti-mouse NeuN (1:100, EMD Millipore, USA), anti-rabbit ROCK 1 (1:100) or anti-rabbit ROCK 2 (1:100, Santa Cruz, USA) [27], anti-mouse cPLA 2 …”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

“…We stained spinal cord neurons with Rho kinase (ROCK 1 or ROCK 2 ) and cPLA 2 antibodies and immunofluorescent secondary antibodies. The images showed that ROCK 1 or ROCK 2 existed in cytoplasm, the same distribution as cytosolic PLA 2 (cPLA 2 ) (Fig.…”

Section: Rock 1 and Rock 2 Two Isoforms Of Rho Kinase Co-localizedmentioning

confidence: 99%

“…Rho kinase (including ROCK 1 and ROCK 2 ) is one of the AGC families of serine-threonine kinases [2]. Rho kinase is a downstream effector of the small GTPase RhoA, which is a major cytoskeleton regulator.…”

Section: Introductionmentioning

confidence: 99%

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RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

Walker

et al. 2016

Mol Neurobiol

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Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A 2 (cPLA 2 ), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10 th thoracic (T10) vertebral level. We found that coadministration of TNF-α and glutamate induced spinal neuron death, and activation of RhoA, Rho kinase and cPLA 2 . Inhibition of RhoA, Rho kinase and cPLA 2 significantly reduced TNF-α/glutamate-induced cell death by 33%, 52% and 43%, respectively (p < 0.001). Inhibition of RhoA and Rho kinase also significantly down-regulated cPLA 2 activation by 66% and 60%, respectively (p < 0.01). Furthermore, inhibition of RhoA and Rho kinase reduced the release of arachidonic acid, a downstream substrate of cPLA 2 . The immunofluorescence staining showed that ROCK 1 or ROCK 2, two isoforms of Rho kinase, was co-localized with cPLA 2 in neuronal cytoplasm. Interestingly, co-immunoprecipitation (Co-IP) assay showed that ROCK 1 or ROCK 2 , bonded directly with cPLA 2 and phospho-cPLA 2 . When the Rho kinase inhibitor Y27632 was applied in mice with T10 contusion injury, it significantly decreased cPLA 2 activation and expression, and reduced injury-induced apoptosis in the lesion area. Taken together, our results reveal a novel mechanism of RhoA/Rho kinase-mediated neuronal death through regulating cPLA 2 activation.

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Section: Rock 1 and Rock 2 Two Isoforms Of Rho Kinase Co-localizedmentioning

confidence: 99%

Section: Combined Insults Of Tnf-α and Glutamate Induced Neurotoxicitmentioning

confidence: 99%

Section: Immunofluorescence Stainingmentioning

confidence: 99%

Section: Rock 1 and Rock 2 Two Isoforms Of Rho Kinase Co-localizedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

Walker

et al. 2016

Mol Neurobiol

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SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK

Shi

Wang

et al. 2022

Molecular Oncology

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Salt-inducible kinase 2 (SIK2; also known as serine/threonine-protein kinase SIK2) is overexpressed in several cancers and has been implicated in cancer progression. However, the mechanisms by which SIK2 regulates cancer cell motility, migration and metastasis in ovarian cancer have not been fully discovered. Here, we identify that SIK2 promotes ovarian cancer cell motility, migration and metastasis in vitro and in vivo. Mechanistically, SIK2 regulated cancer cell motility and migration by myosin light chain kinase, smooth muscle (MYLK)-meditated phosphorylation of myosin light chain 2 (MYL2). SIK2 directly phosphorylated MYLK at Ser343 and activated its downstream effector MYL2, promoting ovarian cancer cell motility and metastasis. In addition, we found that adipocytes induced SIK2 phosphorylation at Ser358 and MYLK phosphorylation at Ser343, enhancing ovarian cancer cell motility. Moreover, SIK2 protein expression was positively correlated with the expression of MYLK-pS343 in ovarian cancer cell lines and tissues. The coexpression of SIK2 and MYLK-pS343 was associated with reduced median overall survival in human ovarian cancer samples. Taken together, SIK2 positively regulates ovarian cancer motility, migration and metastasis, suggesting that SIK2 is a potential candidate for ovarian cancer treatment.

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Benzothiazole derivatives in the design of antitumor agents

Paoletti,

Supuran

2024

Archiv der Pharmazie

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Benzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti‐inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor‐hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual‐specificity protein kinase, cyclin‐dependent protein kinases, casein kinase 2, Rho‐related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase‐2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl‐CoA desaturase, peroxisome proliferator‐activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia‐inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.

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Rho-associated coiled-coil kinase (ROCK) signaling and disease

Cited by 165 publications

References 247 publications

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK

Benzothiazole derivatives in the design of antitumor agents

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