Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells

Kaempchen, Katherine; Mielke, Kirsten; Utermark, Tamara; Langmesser, Sonja; Hanemann, C. Oliver

doi:10.1093/hmg/ddg146

Cited by 108 publications

(106 citation statements)

References 62 publications

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“…The amount of GTP-Cdc42, a closely related small GTPase, was not affected (data not shown), confirming the specificity of NSC23766 Rac inhibitor (Gao et al, 2004). As reported previously (Kaempchen et al, 2003), both activation and expression of Rac1 were significantly higher in schwannoma cells than in normal Schwann cells (Fig. 1 A).…”

Section: Gtp-rac Is Suppressed By Nsc23766 a Rac-specific Inhibitorsupporting

confidence: 88%

“…Schwannoma cells have increased active Rac and its downstream effector p21-activated kinase (PAK) (Kaempchen et al, 2003). NF2 is involved in suppression of Rac-PAK signaling by blocking the p21 binding domain (PBD) of PAK (Kissil et al, 2003) or by binding to Rho-GDI, a GDP dissociation inhibitor, that may stabilize the inactive form of Rac (Maeda et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Temporal Control of Rac in Schwann Cell–Axon Interaction Is Disrupted inNF2-Mutant Schwannoma Cells

Nakai

Zheng²,

MacCollin³

et al. 2006

J. Neurosci.

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Section: Gtp-rac Is Suppressed By Nsc23766 a Rac-specific Inhibitorsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Temporal Control of Rac in Schwann Cell–Axon Interaction Is Disrupted inNF2-Mutant Schwannoma Cells

Nakai

Zheng²,

MacCollin³

et al. 2006

J. Neurosci.

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“…Furthermore, some authors suggest that ERK and JNK activity defines the state of SC differentiation. Whereas basal levels are necessary for differentiation of precursors, high ERK and JNK activities drive dedifferentiation and migration [48][49][50][51][52]. In contrast, the role of the p38 MAPK in SCs is controversial.…”

Section: Discussionmentioning

confidence: 99%

N-cadherin expression is regulated by UTP in schwannoma cells

Martiáñez

Lamarca

Casals

et al. 2012

Purinergic Signalling

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Schwann cells (SCs) are peripheral myelinating glial cells that express the neuronal Ca 2+ -dependent cell adhesion molecule, neural cadherin (N-cadherin). Ncadherin is involved in glia-glia and axon-glia interactions and participates in many key events, which range from the control of axonal growth and guidance to synapse formation and plasticity. Extracellular UTP activates P2Y purinergic receptors and exerts short-and long-term effects on several tissues to promote wound healing. Nevertheless, the contribution of P2Y receptors in peripheral nervous system functions is not completely understood. The current study demonstrated that UTP induced a dose-and timedependent increase in N-cadherin expression in SCs. Furthermore, N-cadherin expression was blocked by the P2 purinoceptor antagonist suramin. The increased N-cadherin expression induced by UTP was mediated by phosphorylation of mitogen-activated protein kinases (MAPKs), such as Jun N-terminal kinase, extracellular-regulated kinase and p38 kinase. Moreover, the Rho kinase inhibitor Y27632, the phospholipase C inhibitor U73122 and the protein kinase C inhibitor calphostin C attenuated the UTP-induced activation of MAPKs significantly. Extracellular UTP also modulated increased in the expression of the early transcription factors c-Fos and c-Jun. We also demonstrated that the region of the N-cadherin promoter between nucleotide positions −3698 and −2620, which contained one activator protein-1-binding site, was necessary for UTP-induced gene expression. These results suggest a novel role for P2Y purinergic receptors in the regulation of N-cadherin expression in SCs.

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“…Extensive research in different cell models suggests that merlin suppresses the Rac/PAK/JNK pathway [18][19][20][21][22]. Therefore, an activation loop between merlin and PAK was suggested [21] and merlin loss would lead to activation of the small GTPases at the membrane [11,23,24].…”

Section: Integrins and Related The Rac/pak/jnk Fak/src And Mtorc1 Pamentioning

confidence: 99%

Merlin, a multi‐suppressor from cell membrane to the nucleus

Zhou

Hanemann

2012

FEBS Letters

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Edited by Wilhelm JustKeywords: NF2 Merlin DCAF1 Integrin RTK a b s t r a c t Recent evidence suggests that the neurofibromatosis type 2 (NF2) gene encoded protein merlin suppresses mitogenic signalling not only at the cell membrane but also in the nucleus. At the membrane, merlin inhibits signalling by integrins and tyrosine receptor kinases (RTKs) and the activation of downstream pathways, including the Ras/Raf/MEK/ERK, FAK/Src, PI3K/AKT, Rac/PAK/ JNK, mTORC1, and Wnt/b-catenin pathways. In the nucleus, merlin suppresses the E3 ubiquitin ligase CRL4 DCAF1 to inhibit proliferation. Gene expression analysis suggested that CRL4 DCAF1 could also regulate the expression of integrins and RTKs. In this review, we explore the links between merlin function at the membrane and in the nucleus, and discuss the potential of targeting the master regulator CRL4 DCAF1 to treat NF2 and other merlin-deficient tumours.

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Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells

Cited by 108 publications

References 62 publications

Temporal Control of Rac in Schwann Cell–Axon Interaction Is Disrupted inNF2-Mutant Schwannoma Cells

Temporal Control of Rac in Schwann Cell–Axon Interaction Is Disrupted inNF2-Mutant Schwannoma Cells

N-cadherin expression is regulated by UTP in schwannoma cells

Merlin, a multi‐suppressor from cell membrane to the nucleus

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