ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion

Anhê, Gabriel Forato; Torrão, Andréa da Silva; Nogueira, Tatiane C.A.; Caperuto, Luciana C.; Amaral, Maria Esméria Corezola do; Medina, Mayrin Correa; Azevedo-Martins, Anna Karenina; Carpinelli, Ângelo Rafael; Carvalho, Carla Roberta de Oliveira; Curi, Rui; Boschero, Antônio Carlos; Bordin, Silvana

doi:10.1016/j.mce.2006.02.012

Cited by 23 publications

(13 citation statements)

References 57 publications

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“…In vitro studies have shown that Erk3 expression is up-regulated during terminal differentiation of model cell lines into neurons or myotubes (3,13). Prolactin treatment also increases Erk3 expression in isolated rat pancreatic islets (14). Altogether, these studies suggest a putative role for Erk3 in regulating cellular differentiation.…”

mentioning

confidence: 82%

Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality

Klinger

Turgeon

Lévesque

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Extracellular signal-regulated kinase 3 (Erk3) is an atypical member of the mitogen-activated protein (MAP) kinase family. No function has yet been ascribed to this MAP kinase. Here we show that targeted disruption of the Mapk6 gene (encoding Erk3) leads to intrauterine growth restriction, associated with marked pulmonary hypoplasia, and early neonatal death during the first day of life. Around 40% of Erk3 ؊/؊ neonates die within minutes after birth from acute respiratory failure. Erk3-deficient mice have normal lung-branching morphogenesis, but show delayed lung maturation characterized by decreased sacculation, atelectasis, and defective type II pneumocyte differentiation. Interestingly, in utero administration of glucocorticoid promoted fetal lung maturity and rescued differentiation of type II cells, but failed to alter the neonatal lethality. We observed that loss of Erk3 retards intrauterine growth, as reflected by a marked reduction in fetal lung, heart, and liver weights, and by low body weight at birth. Importantly, we found that insulin-like growth factor (IGF)-2 levels are decreased in the serum of Erk3-deficient mice. Our findings reveal a critical role for Erk3 in the establishment of fetal growth potential and pulmonary function in the mouse.AP kinases are a family of serine/threonine kinases that play a key role in transducing environmental stimuli into a wide range of intracellular responses (1). In mammals, 14 MAP kinase genes have been identified that define seven distinct MAP kinase signaling pathways (2). The classical MAP kinases are phosphorylated and activated by members of the MAP kinase kinase/Mek family and comprise the well-characterized Erk1/ Erk2, Jnk1/2/3, p38␣/␤/␥/␦, and Erk5 enzymes. Atypical MAP kinases include Erk3/Erk4, NLK, and Erk7. Much less is known about the mechanisms of regulation, substrate specificity, and physiological functions of this latter group of MAP kinases.The Erk3 gene was originally identified by homology-based cloning using the Erk1 cDNA as probe (3). Erk3 exists as a 100-kDa protein consisting of a kinase domain at the N terminus followed by a unique C-terminal extension of unknown function (3-5). Despite the significant homology of their kinase domains, several properties distinguish Erk3 from Erk1/Erk2 and other classical MAP kinases. Erk3 contains a single phospho-acceptor site in the activation loop instead of the canonical dual phosphorylation motif Thr-Xaa-Tyr. Unlike classical MAP kinases, activation loop phosphorylation of Erk3 is detected in resting cells and is minimally modulated by mitogenic or stress stimuli (6). Functionally, Erk3 does not phosphorylate generic MAP kinase substrates such as myelin basic protein [(7); unpublished data], indicating that it has different or more restricted substrate specificity. The only substrate of Erk3 that has been identified so far is the MAP kinase-activated protein kinase MK5 (8, 9). Structurally, Erk3 is most closely related to the MAP kinase Erk4. The two proteins display 73% amino acid identity in the ...

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confidence: 82%

Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality

Klinger

Turgeon

Lévesque

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…According to the manufacturers and selected references [31–34], these antibodies show no cross-reactivity with other MAPs and recognize only its own isoform either as a single band or as a doublet. Briefly, paraffin-embedded MTLE and control hippocampi were processed together for each antibody as described in Kandratavicius et al's work [11], with overnight incubation at room temperature and developed simultaneously for 10 min in 0.05% 3, 3′-diaminobenzidine tetrahydrochloride (Pierce, Rockford, USA) and 0.01% hydrogen peroxide (Merck, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Microtubule-Associated Proteins in Mesial Temporal Lobe Epilepsy with and without Psychiatric Comorbidities and Their Relation with Granular Cell Layer Dispersion

Kandratavicius

Monteiro

Hallak

et al. 2013

BioMed Research International

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Background. Despite strong association between epilepsy and psychiatric comorbidities, biological substrates are unknown. We have previously reported decreased mossy fiber sprouting in mesial temporal lobe epilepsy (MTLE) patients with psychosis and increased in those with major depression. Microtubule associated proteins (MAPs) are essentially involved in dendritic and synaptic sprouting. Methods. MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, and MTLE + interictal psychosis derived from epilepsy surgery and control necropsies were investigated for neuronal density, granular layer dispersion, and MAP2 and tau immunohistochemistry. Results. Altered MAP2 and tau expression in MTLE and decreased tau expression in MTLE with psychosis were found. Granular layer dispersion correlated inversely with verbal memory scores, and with MAP2 and tau expression in the entorhinal cortex. Patients taking fluoxetine showed increased neuronal density in the granular layer and those taking haloperidol decreased neuronal density in CA3 and subiculum. Conclusions. Our results indicate relations between MAPs, granular layer dispersion, and memory that have not been previously investigated. Differential MAPs expression in human MTLE hippocampi with and without psychiatric comorbidities suggests that psychopathological states in MTLE rely on differential morphological and possibly neurochemical backgrounds. This clinical study was approved by our institution's Research Ethics Board (HC-FMRP no. 1270/2008) and is registered under the Brazilian National System of Information on Ethics in Human Research (SISNEP) no. 0423.0.004.000-07.

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“…After centrifugation, equal amounts of protein were resolved by SDS-PAGE, and transferred onto nitrocellulose membranes. Detection using specific antibodies, HRP-conjugated secondary antibodies, and luminol solution was performed as described previously (Anhê et al 2006). …”

Section: Western Blottingmentioning

confidence: 99%

UPR-mediated TRIB3 expression correlates with reduced AKT phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in RINm5F cells

Nicoletti-Carvalho¹,

Nogueira²,

Gorjão³

et al. 2010

Journal of Endocrinology

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Unfolded protein response (UPR)-mediated pancreatic b-cell death has been described as a common mechanism by which palmitate (PA) and pro-inflammatory cytokines contribute to the development of diabetes. There are evidences that interleukin 6 (IL6) has a protective action against b-cell death induced by pro-inflammatory cytokines; the effects of IL6 on PA-induced apoptosis have not been investigated yet. In the present study, we have demonstrated that PA selectively disrupts IL6-induced RAC-alpha serine/threonine-protein kinase (AKT) activation without interfering with signal transducer and activator of transcription 3 phosphorylation in RINm5F cells. The inability of IL6 to activate AKT in the presence of PA correlated with an inefficient protection against PA-induced apoptosis. In contrast to PA, IL6 efficiently reduced apoptosis induced by proinflammatory cytokines. In addition, we have demonstrated that IL6 is unable to overcome PA-stimulated UPR, as assessed by activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) expression, X-box binding protein-1 gene mRNA splicing, and pancreatic eukaryotic initiation factor-2a kinase phosphorylation, whereas no significant induction of UPR by pro-inflammatory cytokines was detected. This unconditional stimulation of UPR and apoptosis by PA was accompanied by the stimulation of CHOP and tribble3 (TRIB3) expression, irrespective of the presence of IL6. These findings suggest that IL6 is unable to protect pancreatic b-cells from PA-induced apoptosis because it does not repress UPR activation. In this way, CHOP and ATF4 might mediate PA-induced TRIB3 expression and, by extension, the suppression of IL6 activation of pro-survival kinase AKT.

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ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion

Cited by 23 publications

References 57 publications

Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality

Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality

Microtubule-Associated Proteins in Mesial Temporal Lobe Epilepsy with and without Psychiatric Comorbidities and Their Relation with Granular Cell Layer Dispersion

UPR-mediated TRIB3 expression correlates with reduced AKT phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in RINm5F cells

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