Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depolarization, growth factors, neurotrophins, and other stimuli induce expression of immediate early genes (IEGs) in neurons. We identified a subset of IEGs, IPD-IEGs, which are induced preferentially by depolarization, but not by neurotrophins or growth factors, in PC12 cells. The "promiscuous" IEGs Egr1 and c-fos, induced by growth factors and neurotrophins, in addition to depolarization, require activation of the MAP kinase signaling pathway for induction in response to KCl depolarization in PC12 cells; MEK1/2 inhibitors block KCl-induced Egr1 and c-fos expression. In contrast, MEK1/2 inhibition has no effect on KCl-induced expression of the known IPD-IEGs in PC12 cells. Additional "candidate" IDP-IEGs were identified by a microarray comparison of genes induced by KCl in the presence vs. the absence of an MEK1/2 inhibitor in PC12 cells. Northern blot analyses demonstrated that representative newly identified candidate IPD-IEGs, as with the known IPD-IEGs, are also induced by a MAP kinase- independent pathway in response to depolarization, both in PC12 cells and in rat primary cortical neurons. Nerve growth factor and epidermal growth factor are unable to induce the expression of the Crem/Icer, Nur77, Nor1, Rgs2, Dusp1 (Mkp1), and Dscr1 genes in PC12 cells, validating their identification as IPD-IEGs. Inhibiting calcium/calmodulin-dependent kinase II (CaMKII), calcineurin, or protein kinase A (PKA) activity prevents KCl-induced IPD-IEG mRNA accumulation, suggesting that the IPD-IEG genes are induced by depolarization in neurons via a combination of calcineurin/PKA- and CaMKII-dependent pathways.
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PMID:The MAPK pathway is required for depolarization-induced "promiscuous" immediate-early gene expression but not for depolarization-restricted immediate-early gene expression in neurons. 1794 Oct 51

Whereas mechanical stimulation is essential for bone homeostasis, straining of larger magnitude promotes bone regeneration by directing cell differentiation and proliferation and influencing the gene expression patterns of osteoblasts, which play a vital role in fracture healing by producing and mineralizing osteoid matrix. To elucidate the molecular mechanisms underlying the response of osteoblasts to mechanical strains comparable to those occurring during bone regeneration, MC3T3 S4 (MC4) osteoblast-like cells were stretched in vitro. Analysis based on microarray expression profiling during the first 8 h after straining showed 674 differentially expressed genes. The response to mechanical strain can be divided in an immediate-early response (IER) and later responses. Examination of the approximately 40 genes differentially expressed within the first 60 min, including 11 involved in regulating gene transcription, showed both promiscuous IER genes such as Fos that are upregulated by multiple extracellular stimuli, as well as a number of genes previously shown in neurons to be induced preferentially by depolarization (IPD-IER). Selected differentially expressed genes were validated after mechanical straining and KCl-induced depolarization. The effects of inhibitors for protein kinase A, mitogen-activated protein kinase, and calcineurin pathways were assessed in separate experiments by quantitative RT-PCR and shown to have differential effects on the response of MC4 cells and primary calvaria osteoblasts to both mechanical straining and KCl-induced depolarization. Therefore, our results showed the existence of two distinct pathways that mediate the IER of osteoblasts to large-magnitude mechanical straining and suggest that the IER to depolarizing stimuli is conserved in cell types as different as osteoblasts and neurons.
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PMID:Promiscuous and depolarization-induced immediate-early response genes are induced by mechanical strain of osteoblasts. 1925 15