Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, it has been shown that cerebellar LTD has a late phase that may be blocked by protein synthesis inhibitors. To understand the mechanisms underlying the late phase, we interfered with the activation of transcription factors that might couple synaptic activation to protein synthesis. Particle-mediated transfection of cultured Purkinje neurons with an expression vector encoding a dominant inhibitory form of CREB resulted in a nearly complete blockade of the late phase. Kinases that activate CREB were inhibited, and LTD was assessed. Inhibition of PKA or the MAPK/RSK cascades were without effect on the late phase, while constructs designed to interfere with CaMKIV function attenuated the late phase. These results indicate that the activation of CaMKIV and CREB are necessary to establish a late phase of cerebellar LTD.
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PMID:A late phase of cerebellar long-term depression requires activation of CaMKIV and CREB. 1043 51

Using the mouse Langendorff heart perfusion model, the signaling pathways that regulate cardiac CREB-S133 phosphorylation have been defined. In mouse hearts stimulated with isoproterenol (ISO) (10(-8) M), endothelin-1 (ET-1) (10(-8) M), and phorbol 12-myristate 13-acetate (TPA) (10(-7) M), CREB-S133 phosphorylation was attained only by TPA-treatment. Activation of protein kinase A (PKA) was achieved by ISO. ISO- and ET-1-stimulation activated Ca2+/calmodulin-dependent kinase II (CaMKII). Protein kinase C (PKC) and p90(RSK) were activated with all three stimuli. Inhibition of ERK1/2 with PD98059 (10(-5) M) completely inhibited the activation of p90(RSK), but did not block CREB-S133 phosphorylation in TPA-perfused heart, indicating that PKA, CaMKII, and p90(RSK) do not phosphorylate CREB-S133 in the murine heart. PKC activation is signal specific. Analyses of PKC isoforms suggest that CREB phosphorylation is mediated by PKC epsilon translocating into nucleus only with TPA stimulation. These results, unlike those reported in other tissues, demonstrate that cardiac CREB is not a multi-signal target.
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PMID:Signaling pathways regulating murine cardiac CREB phosphorylation. 1699 75