Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p74raf-1, a serine/threonine kinase, is structurally related to the protein kinase C (PKC) family and contains a cysteine motif in its N-terminal domain, which is essential for its regulation. It has been shown that p74raf-1 functions upstream of mitogen-activated protein (MAP) kinase kinase. We have constructed a p74raf-1 mutant (N delta raf) that only contains the N-terminal regulatory domain. When transiently expressed in COS-M6 cells, N delta raf efficiently blocked the activation of the MAP extracellular signal regulated kinase (ERK2), induced by either epidermal growth factor, phorbol ester, serum, or oncogenic p21ras. Similar constructs with the cysteine motifs from either PKC-alpha or diacylglycerol kinase did not inhibit activation of ERK2. Overexpression of full-length p74raf-1 rescued the inhibition of ERK2 by N delta raf in a stimulus dependent manner, indicating that N delta raf acts as a competitive inhibitor of wild-type p74raf-1. In contrast, overexpression of either PKC-alpha, -epsilon, or -zeta in N delta raf-containing cells could not rescue the inhibition of ERK2. We conclude that p74raf-1 is an essential mediator of epidermal growth factor- and phorbol ester-induced ERK2 activation and that the MAP kinase kinase activity of p74raf-1 cannot be substituted with either PKC-alpha, -epsilon or -zeta.
 ...
PMID:A dominant-negative mutant of raf blocks mitogen-activated protein kinase activation by growth factors and oncogenic p21ras. 839 1

Leptin is a versatile 16 kDa peptide hormone, with a tertiary structure resembling that of members of the long-chain helical cytokine family. It is mainly produced by adipocytes in proportion to fat size stores, and was originally thought to act only as a satiety factor. However, the ubiquitous distribution of OB-R leptin receptors in almost all tissues underlies the pleiotropism of leptin. OB-Rs belong to the class I cytokine receptor family, which is known to act through JAKs (Janus kinases) and STATs (signal transducers and activators of transcription). The OB-R gene is alternatively spliced to produce at least five isoforms. The full-length isoform, OB-Rb, contains intracellular motifs required for activation of the JAK/STAT signal transduction pathway, and is considered to be the functional receptor. Considerable evidence for systemic effects of leptin on body mass control, reproduction, angiogenesis, immunity, wound healing, bone remodelling and cardiovascular function, as well as on specific metabolic pathways, indicates that leptin operates both directly and indirectly to orchestrate complex pathophysiological processes. Consistent with leptin's pleiotropic role, its participation in and crosstalk with some of the main signalling pathways, including those involving insulin receptor substrates, phosphoinositide 3-kinase, protein kinase B, protein kinase C, extracellular-signal-regulated kinase, mitogen-activated protein kinases, phosphodiesterase, phospholipase C and nitric oxide, has been observed. The impact of leptin on several equally relevant signalling pathways extends also to Rho family GTPases in relation to the actin cytoskeleton, production of reactive oxygen species, stimulation of prostaglandins, binding to diacylglycerol kinase and catecholamine secretion, among others.
 ...
PMID:Intracellular signalling pathways activated by leptin. 1633 96