Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.25 (MEKK1)
1,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular signals are transduced into cells through mitogen-activated protein kinases (MAPKs), which are activated by their upstream kinases. Recently, families of scaffolding proteins have been identified to tether specific combinations of these kinases along specific signaling pathways. Here we describe a protein, JLP (c-Jun NH2-terminal kinase-associated leucine zipper protein), which acts as a scaffolding protein to bring together Max and c-Myc along with JNK (c-Jun NH2-terminal kinase) and p38MAPK, as well as their upstream kinases MKK4 (MAPK kinase 4) and MEKK3 (MAPK kinase kinase 3). Thus, JLP defines a family of scaffolding proteins that bring MAPKs and their target transcription factors together for the execution of specific signaling pathways.
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PMID:JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors. 1239 7

Mitogen-activated protein (MAP) kinase signaling cascades orchestrate diverse cellular activities with common molecular players. To achieve specific cellular outcomes in response to specific signals, scaffolding proteins play an important role. Here we investigate the role of the scaffolding protein JNK interacting protein-1 (JIP1) in neuronal signaling by a conserved axonal MAP kinase kinase kinase, known as Wallenda (Wnd) in Drosophila and dual leucine kinase (DLK) in vertebrates and Caenorhabditis elegans. Recent studies in multiple model organisms suggest that Wnd/DLK regulates both regenerative and degenerative responses to axonal injury. Here we report a new role for Wnd in regulating synaptic structure during development, which implies that Wnd is also active in uninjured neurons. This synaptic role of Wnd can be functionally separated from the role of Wnd in axonal regeneration and injury signaling by the requirement for the JIP1 scaffold and the p38b MAP kinase. JIP1 mediates the synaptic function of Wnd via p38, which is not required for injury signaling or new axonal growth after injury. Our results indicate that Wnd regulates multiple independent pathways in Drosophila motoneurons and that JIP1 scaffolds a specific downstream cascade required for the organization of presynaptic microtubules during synaptic development.
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PMID:Independent pathways downstream of the Wnd/DLK MAPKKK regulate synaptic structure, axonal transport, and injury signaling. 2390 12