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???displayArticle.abstract??? Nerve growth factor (NGF) promotes neuronal survival and differentiation by activating TrkA receptors. Similar to other receptor tyrosine kinases, ligand-induced dimerization is thought to be required for TrkA receptor activation. To study this process, we expressed TrkA receptors in Xenopus laevis oocytes and analyzed their response to NGF by using a combination of functional, biochemical, and structural approaches. TrkA receptor protein was detected in the membrane fraction of oocytes injected with TrkA receptor cRNA, but not in uninjected or mock-injected oocytes. Application of NGF to TrkA receptor-expressing oocytes promoted tyrosine phosphorylation and activated an oscillating transmembrane inward current, indicating that the TrkA receptors were functional. Freeze-fracture electron microscopic analysis demonstrated novel transmembrane particles in the P-face (protoplasmic face) of oocytes injected with TrkA cRNA, but not in uninjected or mock injected oocytes. Incubating TrkA cRNA-injected oocytes with the transcriptional inhibitor actinomycin D did not prevent the appearance of these P-face particles or electrophysiological responses to NGF, demonstrating that they did not arise from de novo transcription of an endogenous Xenopus oocyte gene. The appearance of these particles in the plasma membrane correlated with responsiveness to NGF as detected by electrophysiological analysis and receptor phosphorylation, indicating that these novel P-face particles were TrkA receptors. The dimensions of these particles (8.6 x 10 nm) were too large to be accounted for by TrkA monomers, suggesting the formation of TrkA receptor oligomers. Application of NGF did not lead to a discernible change in the size or shape of these TrkA receptor particles during an active response. These results indicate that in Xenopus oocytes, NGF activates signaling via pre-formed TrkA receptor oligomers.
Arevalo,
TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor.
2000, Pubmed
Arevalo,
TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor.
2000,
Pubmed
Barbacid,
Structural and functional properties of the TRK family of neurotrophin receptors.
1995,
Pubmed
Branton,
Fracture faces of frozen membranes.
1966,
Pubmed
Burke,
Activation of Neu (ErbB-2) mediated by disulfide bond-induced dimerization reveals a receptor tyrosine kinase dimer interface.
1998,
Pubmed
Burke,
Dimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation.
1997,
Pubmed
Callamaras,
Ca(2+)-dependent activation of Cl(-) currents in Xenopus oocytes is modulated by voltage.
2000,
Pubmed
,
Xenbase
Carriero,
Structure and expression of the nerve growth factor gene in Xenopus oocytes and embryos.
1991,
Pubmed
,
Xenbase
Clary,
TrkA cross-linking mimics neuronal responses to nerve growth factor.
1994,
Pubmed
Cochet,
Demonstration of epidermal growth factor-induced receptor dimerization in living cells using a chemical covalent cross-linking agent.
1988,
Pubmed
Connolly,
Regulation of growth cone morphology by nerve growth factor: a comparative study by scanning electron microscopy.
1985,
Pubmed
Eskandari,
Number of subunits comprising the epithelial sodium channel.
1999,
Pubmed
,
Xenbase
Eskandari,
Pentameric assembly of a neuronal glutamate transporter.
2000,
Pubmed
,
Xenbase
Eskandari,
Structural analysis of cloned plasma membrane proteins by freeze-fracture electron microscopy.
1998,
Pubmed
,
Xenbase
Gadella,
Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine kinase receptor activation.
1995,
Pubmed
Hartzell,
Activation of different Cl currents in Xenopus oocytes by Ca liberated from stores and by capacitative Ca influx.
1996,
Pubmed
,
Xenbase
Heldin,
Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation.
1989,
Pubmed
Hempstead,
High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor.
1991,
Pubmed
Holden,
Immunoglobulin-like domains define the nerve growth factor binding site of the TrkA receptor.
1997,
Pubmed
Inui,
Transduction of mitogenic activity of platelet-derived growth factor (PDGF) AB by PDGF-beta receptor without participation of PDGF-alpha receptor in vascular smooth muscle cells.
1993,
Pubmed
Jiang,
Receptor signaling: when dimerization is not enough.
,
Pubmed
Jing,
Nerve growth factor mediates signal transduction through trk homodimer receptors.
1992,
Pubmed
Kaplan,
Neurotrophin signal transduction by the Trk receptor.
1994,
Pubmed
Kaplan,
Neurotrophin signal transduction in the nervous system.
2000,
Pubmed
Klein,
The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3.
1991,
Pubmed
Klesse,
Trks: signal transduction and intracellular pathways.
,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Livnah,
Functional mimicry of a protein hormone by a peptide agonist: the EPO receptor complex at 2.8 A.
1996,
Pubmed
Livnah,
Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation.
1999,
Pubmed
Livnah,
An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation.
1998,
Pubmed
Loeb,
A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-gamma 1 abolishes NGF-promoted peripherin induction but not neurite outgrowth.
1994,
Pubmed
Maliartchouk,
Genuine monovalent ligands of TrkA nerve growth factor receptors reveal a novel pharmacological mechanism of action.
2000,
Pubmed
Maliartchouk,
A designed peptidomimetic agonistic ligand of TrkA nerve growth factor receptors.
2000,
Pubmed
McDonald,
New protein fold revealed by a 2.3-A resolution crystal structure of nerve growth factor.
1991,
Pubmed
Meakin,
Molecular investigations on the high-affinity nerve growth factor receptor.
1991,
Pubmed
Mischel,
The extracellular domain of p75NTR is necessary to inhibit neurotrophin-3 signaling through TrkA.
2001,
Pubmed
,
Xenbase
Nebreda,
Induction by NGF of meiotic maturation of Xenopus oocytes expressing the trk proto-oncogene product.
1991,
Pubmed
,
Xenbase
Obermeier,
Tyrosine 785 is a major determinant of Trk--substrate interaction.
1993,
Pubmed
Remy,
Erythropoietin receptor activation by a ligand-induced conformation change.
1999,
Pubmed
Schlessinger,
Growth factor signaling by receptor tyrosine kinases.
1992,
Pubmed
Segal,
Intracellular signaling pathways activated by neurotrophic factors.
1996,
Pubmed
Sehgal,
Efficient processing and expression of human nerve growth factor receptors in Xenopus laevis oocytes: effects on maturation.
1988,
Pubmed
,
Xenbase
Sternberg,
A sequence motif in the transmembrane region of growth factor receptors with tyrosine kinase activity mediates dimerization.
1990,
Pubmed
Treanor,
Heterodimeric neurotrophins induce phosphorylation of Trk receptors and promote neuronal differentiation in PC12 cells.
1995,
Pubmed
Umbach,
Expression of an omega-conotoxin-sensitive calcium channel in Xenopus oocytes injected with mRNA from Torpedo electric lobe.
1987,
Pubmed
,
Xenbase
Umbach,
Alpha-latrotoxin triggers an increase of ionized calcium in Xenopus oocytes injected with rat brain mRNA.
1990,
Pubmed
,
Xenbase
Weber,
Endogenous ion channels in oocytes of xenopus laevis: recent developments.
1999,
Pubmed
,
Xenbase
Wiesmann,
Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor.
1999,
Pubmed
Wion,
Synthesis and partial maturation of the alpha- and gamma-subunits of the mouse submaxillary gland nerve growth factor in Xenopus laevis oocytes.
1984,
Pubmed
,
Xenbase
Wiseman,
Image correlation spectroscopy. II. Optimization for ultrasensitive detection of preexisting platelet-derived growth factor-beta receptor oligomers on intact cells.
1999,
Pubmed
Woo,
Characterization of the recombinant extracellular domain of the neurotrophin receptor TrkA and its interaction with nerve growth factor (NGF).
1998,
Pubmed
Zaccaro,
p75 Co-receptors regulate ligand-dependent and ligand-independent Trk receptor activation, in part by altering Trk docking subdomains.
2001,
Pubmed
Zampighi,
A method for determining the unitary functional capacity of cloned channels and transporters expressed in Xenopus laevis oocytes.
1995,
Pubmed
,
Xenbase
Zampighi,
Functional and morphological correlates of connexin50 expressed in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase
