scholarly journals Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho/TLE:Hes1-mediated inhibition of neuronal differentiation

2013 ◽  
Vol 21 (2) ◽  
pp. 321-332 ◽  
Author(s):  
R Ciarapica ◽  
L Methot ◽  
Y Tang ◽  
R Lo ◽  
R Dali ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Neuronal Differentiation ◽  
Prolyl Isomerase ◽  
Cortical Neurogenesis

Regulation of protein kinase C activity in neuronal differentiation induced by the N-ras oncogene in PC-12 cells

1990 ◽  
Vol 10 (6) ◽  
pp. 2983-2990
Author(s):  
J C Lacal ◽  
A Cuadrado ◽  
J E Jones ◽  
R Trotta ◽  
D E Burstein ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Neuronal Differentiation ◽  
Phorbol Esters ◽  
Ras Oncogene ◽  
Intact Cells ◽  
Pc 12 Cells ◽  
Kinase C ◽  
Ras P21

Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be functional.

Neuronal Differentiation of PC12 Cells Involves Changes in Protein Kinase C-θ Distribution and Molecular Properties

2000 ◽  
Vol 275 (1) ◽  
pp. 149-153 ◽  
Author(s):  
Bianca Sparatore ◽  
Mauro Patrone ◽  
Mario Passalacqua ◽  
Marco Pedrazzi ◽  
Sandro Pontremoli ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Molecular Properties ◽  
Kinase C

scholarly journals Phosphorylation of Ago2 and Subsequent Inactivation of let-7a RNP-Specific MicroRNAs Control Differentiation of Mammalian Sympathetic Neurons

2016 ◽  
Vol 36 (8) ◽  
pp. 1260-1271 ◽  
Author(s):  
Somi Patranabis ◽  
Suvendra Nath Bhattacharyya
Keyword(s):  
Protein Kinase ◽  
Neuronal Differentiation ◽  
Sympathetic Neurons ◽  
Neuronal Cells ◽  
Cellular Level ◽  
Mitogen Activated Protein Kinase ◽  
Animal Cells ◽  
Mitogen Activated Protein ◽  
Small Regulatory Rnas ◽  
Necessary And Sufficient

MicroRNAs (miRNAs) are small regulatory RNAs that regulate gene expression posttranscriptionally by base pairing to the target mRNAs in animal cells.KRas, an oncogene known to be repressed by let-7a miRNAs, is expressed and needed for the differentiation of mammalian sympathetic neurons and PC12 cells. We documented a loss of let-7a activity during this differentiation process without any significant change in the cellular level of let-7a miRNA. However, the level of Ago2, an essential component that is associated with miRNAs to form RNP-specific miRNA (miRNP) complexes, shows an increase with neuronal differentiation. In this study, differentiation-induced phosphorylation and the subsequent loss of miRNA from Ago2 were noted, and these accounted for the loss of miRNA activity in differentiating neurons. Neuronal differentiation induces the phosphorylation of mitogen-activated protein kinase p38 and the downstream kinase mitogen- and stress-activated protein kinase 1 (MSK1). This in turn upregulates the phosphorylation of Ago2 and ensures the dissociation of miRNA from Ago2 in neuronal cells. MSK1-mediated miRNP inactivation is a prerequisite for the differentiation of neuronal cells, where let-7a miRNA gets unloaded from Ago2 to ensure the upregulation ofKRas, a target of let-7a. We noted that the inactivation of let-7a is both necessary and sufficient for the differentiation of sympathetic neurons.

scholarly journals Pituitary Adenylate Cyclase-Activating Polypeptide 38-Mediated Rin Activation Requires Src and Contributes to the Regulation of Hsp27 Signaling during Neuronal Differentiation

2008 ◽  
Vol 28 (16) ◽  
pp. 4940-4951 ◽  
Author(s):  
Geng-Xian Shi ◽  
Ling Jin ◽  
Douglas A. Andres
Keyword(s):  
Protein Kinase ◽  
Adenylate Cyclase ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Function Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascades ◽  
Critical Element ◽  
Dependent Manner ◽  
Pituitary Adenylate Cyclase

ABSTRACT Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a potent neuropeptide that acts through G-protein-coupled receptors. While it is well established that PACAP mediates both neurotrophic and neurodevelopmental effects, the signaling cascades that underlie these diverse actions remain incompletely characterized. Here we show that the Ras-related Rin GTP-binding protein, a GTPase that is expressed predominantly in neurons, is regulated by PACAP38 signaling, and loss-of-function analysis demonstrates that Rin makes an essential contribution to PACAP38-mediated pheochromocytoma cell differentiation. Rin is activated following stimulation of both Gsα and Giα cascades but does not rely upon cyclic AMP (cAMP)-, Ca2+-, or Epac-dependent signaling pathways. Instead, Rin is activated in a Src kinase-dependent manner. Surprisingly, Rin knockdown significantly inhibits PACAP38-mediated neurite outgrowth, without affecting mitogen-activated protein kinase signaling cascades. Instead, Rin loss attenuates PACAP38-mediated HSP27 activation by disrupting a cAMP-protein kinase A cascade. RNA interference-mediated HSP27 silencing suppresses both PACAP38- and Rin-mediated neurite outgrowth, while expression of a constitutively active Rin mutant increases both HSP27 protein and phospho-HSP27 levels, supporting a role for Rin-HSP27 signaling in neuronal differentiation. Together, these observations identify an unsuspected role for Rin in neuronal PACAP signaling and establish a novel Gα-Src-Rin-HSP27 signal transduction pathway as a critical element in PACAP38-mediated neuronal differentiation signaling.

scholarly journals Prolyl Isomerase Pin1 Negatively Regulates AMP-activated Protein Kinase (AMPK) by Associating with the CBS Domain in the γ Subunit

2015 ◽  
Vol 290 (40) ◽  
pp. 24255-24266 ◽  
Author(s):  
Yusuke Nakatsu ◽  
Misaki Iwashita ◽  
Hideyuki Sakoda ◽  
Hiraku Ono ◽  
Kengo Nagata ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Prolyl Isomerase ◽  
Cbs Domain ◽  
Γ Subunit ◽  
Amp Activated Protein Kinase

scholarly journals WNT/B-catenin dependant alteration of cortical neurogenesis in a human stem cell model of SETBP1 disorder

2021 ◽  
Author(s):  
Lucia F Cardo ◽  
Meng Li
Keyword(s):  
Neuronal Differentiation ◽  
Cell Model ◽  
Embryonic Stem ◽  
Autistic Traits ◽  
Transcriptome Profiling ◽  
Loss Of Function ◽  
Cortical Neurogenesis ◽  
Severe Intellectual Disability ◽  
Genome Wide

Disruptions of SETBP1 (SET binding protein 1) on 18q12.3 by heterozygous gene deletion or loss-of-function variants cause SETBP1 disorder. Clinical features are frequently associated with moderate to severe intellectual disability, autistic traits and speech and motor delays. Despite SETBP1 association with neurodevelopmental disorders, little is known about its role in brain development. Using CRISPR/CAS9 genome editing technology, we generated a SETBP1 deletion model in human embryonic stem cells (hESCs), and examined the effects of SETBP1-deficiency in in vitro derived neural progenitors (NPCs) and neurons using a battery of cellular assays, genome wide transcriptomic profiling and drug-based phenotypic rescue. SETBP1-deficient NPCs exhibit protracted proliferation and distorted layer-specific neuronal differentiation with overall decrease in neurogenesis. Genome wide transcriptome profiling and protein biochemical analysis showed that SETBP1 deletion led to enhanced activation of WNT/B-catenin signaling. Crucially, treatment of the SETBP1-deficient NPCs with a small molecule WNT inhibitor XAV939 restored hyper canonical B-catenin activity and rescued cortical neuronal differentiation. Our study establishes a novel regulatory link between SETBP1 and WNT/B-catenin signaling during human cortical neurogenesis and provides mechanistic insights into structural abnormalities and potential therapeutic avenues for SETBP1 disorder.

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