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Nerve growth factor (NGF) is a member of an expanding family of neurotrophic factors (including brain-derived neurotrophic factor and the neurotrophins) that control the development and survival of certain neuronal populations both in the peripheral and in the central nervous systems. Its biological effects are mediated by a high-affinity ligand-receptor(More)
Recent studies on nerve growth factor have revealed important new insights into the structure, function and evolution of this prototypical neurotrophic factor. Some of its features are (1) it has a unique three-dimensional fold that has since been found in two other growth factors, (2) it uses the trk proto-oncogene product, which has a tyrosine kinase, as(More)
Ligand-induced receptor oligomerization is a widely accepted mechanism for activation of cell-surface receptors. We investigated ligand-receptor interactions in the glial cell-line derived neurotrophic factor (GDNF) receptor complex, formed by the c-Ret receptor tyrosine kinase and the glycosylphosphatidylinositol (GPI)-anchored subunit GDNF family receptor(More)
Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA) are endogenously produced amino acids that inhibit all three isoforms of nitric oxide synthase (NOS). ADMA accumulates in various disease states, including renal failure, diabetes and pulmonary hypertension, and its concentration in plasma is strongly predictive of premature cardiovascular(More)
Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives of arginine whose cellular levels are controlled in part by dimethylarginine dimethylaminohydrolase (DDAH, EC Levels of asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with certain disease states. Here, the first structure of a DDAH shows an unexpected(More)
F-box proteins are the substrate-recognition components of the Skp1-Cul1-F box protein (SCF) E3 ubiquitin ligases. Here we report a structural relationship between Fbxo7, a component of the SCF(Fbxo7) E3 ligase, and the proteasome inhibitor PI31. SCF(Fbxo7) is known to catalyze the ubiquitination of hepatoma-up-regulated protein (HURP) and the inhibitor of(More)
The RET proto-oncogene encodes a receptor tyrosine kinase for the glial cell line-derived neurotrophic factor family of ligands. Loss-of-function mutations in RET are implicated in Hirschsprung disease, whereas activating mutations in RET are found in human cancers, including familial medullar thyroid carcinoma and multiple endocrine neoplasias 2A and 2B.(More)
The protein kinase C (PKC) family is represented in all eukaryotes and in Homo sapiens comprises the related PKCα through PKCι gene products (Dempsey et al., 2000). The kinase domains are closely related, as illustrated in the dendrogram, and form part of the AGC kinase superfamily. For clarity, the PKC-related kinases (PRK/PKN) are not included here;(More)
BACKGROUND The protein kinase C (PKC) family of lipid-dependent serine/theonine kinases plays a central role in many intracellular eukaryotic signalling events. Members of the novel (delta, epsilon, eta, theta) subclass of PKC isotypes lack the Ca2+ dependence of the conventional PKC isotypes and have an N-terminal C2 domain, originally defined as V0(More)
Nerve growth factor (NGF), like many other growth factors and hormones, binds to two different receptor molecules on responsive cells. The product of the proto-oncogene trk, p140trk, is a tyrosine kinase receptor that has been identified as a signal-transducing receptor for NGF, while the role of the low affinity NGF receptor, p75NGFR, in signal(More)