Molecular analysis of the human trk oncogene, a transforming gene isolated from colon carcinoma biopsy, revealed existence novel member tyrosine kinase family. This locus, which we now designate proto-oncogene, codes for protein 790 amino acid residues that has several features characteristic cell surface receptors. They include (i) 32-amino-acid-long putative signal peptide, (ii) an amino-terminal moiety (residues 33 to 407) rich in consensus sites N-glycosylation, (iii) transmembrane...

A single genetic alteration, a guanine-to-cytosine transversion, is responsible for the acquisition of malignant properties by K-ras genes two human tumor cell lines established from carcinomas bladder (A1698) and lung (A2182). As consequence, arginine instead normal glycine incorporated into K-ras-coded p21 proteins at amino acid position 12. This mutation creates restriction enzyme polymorphism that can be used to screen cells transforming genes. approach was identify mutational event...

Abstract We have examined the expression of trkB gene, which encodes a member family protein tyrosine kinase (TK) transmembrane receptors, during mouse embryogenesis using in situ hybridization and Northern analysis. Transcripts were first detected neuroepithelium neural crest 9.5 day embryos with regions high folds at lateral neuroepithelium. However, process cephalization development peripheral nervous system, transcripts most tissues, including brain, spinal cord, cranial ganglia, along...

We have cloned and characterized the mouse homolog of human trk proto-oncogene, a member protein tyrosine kinase (TK) receptor gene family. Here, we present first report trk-encoded mRNA species in vivo. In situ hybridization analysis embryo reveals striking temporal spatial regulation transcription, with expression confined to sensory cranial (trigeminal, superior, jugular) dorsal root ganglia (DRG) neural crest origin. Recent reports shown that TK receptors can play regulatory roles...

ABSTRACT The Trk family of tyrosine kinases encodes receptors for nerve growth factor-related neurotrophins. Here we present a developmental expression study trkC, which receptor neurotrophin-3 (NT-3). Like the related genes, trk and trkB, trkC is expressed primarily in neural lineages although pattern complex includes non-neuronal cells. Direct comparison with trkB patterns permits following observations. (1) novel tissues where other genes are silent. (2) Some appear to coexpress embryo...

Nerve growth factor (NGF) promotes the survival and differentiation of specific populations neurons. The molecular mechanisms by which cells respond to NGF are poorly understood, but two clues have emerged recently. First, rapidly stimulates tyrosine phosphorylation several unidentified proteins in NGF-responsive pheochromocytoma cell line PC12 [Maher, P. (1988) Proc. Natl. Acad. Sci. USA 85, 6788-6791]. Second, protein-tyrosine kinase encoded protooncogene trk (p140trk), a member receptor...

The effect of nerve growth factor (NGF) was assessed in Xenopus oocytes expressing the human trk proto-oncogene product, p140prototrk. Oocytes injected with messenger RNA expressed polypeptides recognized by antibodies to gene product. Exposure these nanomolar amounts NGF resulted specific surface binding 125I-labeled NGF, tyrosine phosphorylation p140prototrk, and meiotic maturation, as determined germinal vesicle breakdown maturation promoting (p34cdc2) kinase activation. Thus product can...

Molecular analysis of the human trk oncogene, a transforming gene isolated from colon carcinoma biopsy, revealed existence novel member tyrosine kinase family. This locus, which we now designate proto-oncogene, codes for protein 790 amino acid residues that has several features characteristic cell surface receptors. They include (i) 32-amino-acid-long putative signal peptide, (ii) an amino-terminal moiety (residues 33 to 407) rich in consensus sites N-glycosylation, (iii) transmembrane...

Abstract : Chick embryo spinal cord motoneurons develop a trophic response to some neurotrophins when they are maintained in culture the presence of muscle extract. Thus, after 2 days culture, brain‐derived neurotrophic factor (BDNF) promotes motoneuron survival. In present study we have analyzed intracellular pathways that may be involved BDNF‐induced We observed BDNF activated extracellular‐regulated kinase (ERK) mitogen‐activated protein (MAP) and phosphatidylinositol (Pl) 3‐kinase...

The extracellular region of the nerve growth factor (NGF) receptor, TrkA, contains two immunoglobulin (Ig)-like domains that are required for specific ligand binding. We have investigated possible role these Ig-like in receptor dimerization and activation by using different mutants TrkA region. Deletions each domain, both, entire were made. To probe structural constraints on ligand-independent dimerization, chimeric receptors generated swapping third or fourth domain c-Kit. also introduced...

The extracellular domain of several membrane-anchored proteins can be released as a soluble fragment by the action cell surface endoproteolytic system. This cleavage results in generation and cell-bound fragment. In case with signaling capability, such tyrosine kinase receptors, process may have an effect on activity receptor By using lines that express TrkA neurotrophin receptor, we show this is cleaved proteolytic system mimics one acts at surface. regulated protein C agonists (including...

Abstract Peroxynitrite is usually considered as a neurotoxic nitric oxide‐derivative. However, an increasing body of evidence suggests that, at low concentrations, peroxynitrite affords transient cytoprotection, both in vitro and vivo . Here, we addressed the signaling mechanism responsible for this effect, found that rat cortical neurons primary culture acutely exposed to (0.1 mmol/L) rapidly elicited Akt‐Ser 473 phosphorylation. Inhibition phosphoinositide‐3‐kinase (PI3K)/Akt pathway with...

Nerve growth factor (NGF) induces survival and differentiation of the neural crest-derived PC12 cell line. Caveolae are cholesterol-enriched, caveolin-containing plasma membrane microdomains involved in vesicular transport signal transduction. Here we demonstrate presence caveolae cells their involvement NGF signaling. Our results showed expression caveolin-1 by Western blot confocal immuno-microscopy. The was directly shown rapid-freeze deep-etching electron microscopy. Moreover, combined...