Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipopolysaccharide (LPS) and muramyl dipeptide (MDP) are components of bacterial cell walls that cause innate immune responses and inflammation. Toll-like receptor 4 (TLR4) is a receptor for LPS and transduces signals through myeloid differentiation factor 88 (MyD88), which plays essential roles in the TLR/interleukin (IL)-1R signaling and activates MAP/ERK kinase (MEK)/ERK pathway to induce receptor activator of NF-kappaB ligand (RANKL) expression in osteoblasts. Osteoblasts express nucleotide oligomerization domain (NOD)2, an intracellular sensor for MDP, in response to LPS, IL-1 and TNF. NOD2 binds receptor-interacting protein (RIP2), a serine/threonine kinase which transduces NF-kappaB signaling. MDP synergistically enhances osteoclast formation induced by LPS, IL-1 and TNF through RANK ligand up-regulation in osteoblasts. TLR4 and NOD2 recognize bacterial components on cell surfaces and inside cells, respectively, and these signals up-regulate RANKL expression in osteoblasts, which results in enhancing osteoclast formation and function.
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PMID:[Bone destruction caused by osteoclasts]. 1646 24

Nod1 is a member of the NLR/Nod/CATERPILLER family. It acts as a sensor for intracellular bacteria by recognizing specific glycopeptides derived from peptidoglycan. Nod1 activation mediates distinct cellular responses including activation of MAP kinases, IL-8 release, apoptosis and suppression of several estrogen-dependent responses in MCF-7 cells. Here we have extended these studies by identifying key regulatory steps in Nod1-dependent signaling pathways. We provide multiple lines of data showing that Nod1-dependent apoptosis is a caspase 8-mediated event and that apoptosis requires RIP2. In contrast, several lines of evidence show that Nod1-dependent JNK activation and IL-8 production did not require the presence of caspase 8 but required activation of TAK1 as well as RIP2. Thus, we have identified several key control points that lie downstream of Nod1. This work provides the basis for further studies of the biological significance and regulation of the Nod1 pathway.
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PMID:Regulation of Nod1-mediated signaling pathways. 1718 25