Autonomic dysreflexia is a condition that develops after spinal cord injury in which potentially life-threatening episodic hypertension triggered by stimulation of sensory nerves the body below site injury. Central sprouting small-diameter primary afferent fibers dorsal horn occurs concurrently with development this condition. We propose model for autonomic increased nerve growth factor (NGF) injured stimulates fiber sprouting, thereby magnifying sympathetic reflexes and promoting...

The trkA receptor functions as a signal transducing for nerve growth factor. In this report, we show that alternative splicing results in the production of two distinct isoforms both rats and humans. These differ by virtue 6-amino acid insertion their extracellular domain, placement which corresponds exactly with breakpoint found several human oncogenes. When tested fibroblasts, presence (trkAII) or absence (trkAI) insert does not affect receptor's ligand binding specificity its ability to...

Two distinct nerve growth factor receptor (NGFR) complexes are present on NGF-responsive cell types; these correspond to 100 kDa and 158 for the fast (fNGFR) slow (sNGFR) NGFRs, respectively. Previous studies indicate that each complex is derived from a separate gene product sNGFR contains tyrosine kinase activity. The cDNA encoding fNGFR has previously been cloned. In this report, rat trk protooncogene isolated PC12 cells Trk shown bind NGF, generating of kDa. Characterization NGF-Trk...

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading irreversible damage. Chemical exchange saturation transfer (CEST) effects can be used generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been delineate the ischemic penumbra after stroke. In current study, a novel MRI ratiometric technique presented measure absolute using ratio...

Neuronal cell fate decisions are directed in Drosophila by NUMB, a signaling adapter protein with two protein–protein interaction domains: phosphotyrosine-binding domain and proline-rich region (PRR) that functions as an SH3-binding domain. Here we show there at least four human NUMB isoforms these serve distinct developmental the neuronal lineage: differentiation (but not proliferation) is promoted type I (short) PRR. In contrast, proliferation differentiation) have II (long) The types of...

We have characterized five human gamma-crystallin genes isolated from a genomic phage library. DNA sequencing of four the revealed that two them predict polypeptides 174 residues showing 71% homology in their amino acid sequence; other correspond to closely related pseudogenes which contain same in-frame termination codon at identical positions coding sequence. Two and one are oriented head-to-tail fashion clustered within 22.5 kilobases. All three TATA box 60 80 base pairs upstream...

Neurotrophins signal via Trk tyrosine kinase receptors and a common receptor called p75. Nerve growth factor is the cognate ligand for TrkA, brain-derived neurotrophic TrkB, neurotrophin-3 (NT-3) TrkC. NT-3 also binds TrkA TrkB as heterologous ligand. All neurotrophins bind p75, which regulates affinity signals. extracellular domain has five subdomains: leucine-rich motif, two cysteine-rich clusters, immunoglobulin-like subdomains IgG-C1 IgG-C2. The subdomain surface exposed in tertiary...

While only two gamma-crystallins have been identified in the human eye lens, molecular studies indicate that are encoded a multigene family comprising at least seven closely related members. Sequence analysis of five these genes has suggested three (gamma 1-2, G3, and G4) potentially active, while (G1 psi G2 psi) correspond to pseudogenes. Here we report on detailed structure sixth gamma-crystallin gene, G5, our results obtained with transient expression assays characterize both promoter...

Ectopic expression of the TrkA receptor tyrosine kinase in tumors nervous system can mediate nerve growth factor (NGF)-dependent cell death by apoptosis and /or autophagy. Herein, we demonstrate that also induce medulloblastoma Daoy cells a caspase-independent mechanism involves hyperstimulation macropinocytosis. Specifically, NGF-stimulates uptake AlexaFluor546-dextran into lysosome-associated membrane protein-1 positive vacuoles which fuse with microtubule associated protein light chain 3...

We have characterized five human gamma-crystallin genes isolated from a genomic phage library. DNA sequencing of four the revealed that two them predict polypeptides 174 residues showing 71% homology in their amino acid sequence; other correspond to closely related pseudogenes which contain same in-frame termination codon at identical positions coding sequence. Two and one are oriented head-to-tail fashion clustered within 22.5 kilobases. All three TATA box 60 80 base pairs upstream...

Alzheimer's disease (AD) is characterized by the deposition of Beta-Amyloid (Aβ) peptides in brain. Aβ are generated cleavage Amyloid Precursor Protein (APP) β - and γ secretase enzymes. Although this process tightly linked to internalization cell surface APP, compartments responsible not well defined. We have found that APP can be rapidly internalized from lysosomes, bypassing early late endosomes. Here we show confocal microscopy electron pathway mediated macropinocytosis. enhanced...

Increased lactate production through glycolysis in aerobic conditions is a hallmark of cancer. Some anticancer drugs have been designed to exploit elevated cancer cells. For example, lonidamine (LND) inhibits transport, leading intracellular acidification Chemical exchange saturation transfer (CEST) novel MRI contrast mechanism that dependent on pH. Amine and amide concentration‐independent detection (AACID) apparent proton (APT*) represent two recently developed CEST parameters are...

Increased intraspinal nerve growth factor (NGF) after spinal cord injury (SCI) is detrimental to the autonomic nervous system. Autonomic dysreflexia a debilitating condition characterized by episodic hypertension, intense headache, and sweating. Experimentally, it associated with aberrant primary afferent sprouting in dorsal horn that (NGF)-dependent. Therapeutic strategies neutralize NGF may ameliorate initial apoptotic cellular responses plasticity occurs weeks injury. Subsequently,...

Activation of the neurotrophin Trk receptors is a key process in survival and development nervous system. The signaling adapters ShcB ShcC, but not ShcA, are thought to be primary Shc adaptor proteins neurons as both highly expressed developing adult Although previous study suggested that ShcC do strongly interact with (1), we find bind phosphotyrosine-dependent manner via their N-terminal phosphotyrosine binding domain at Tyr⁴⁹⁹ (TrkA) Tyr⁵¹⁵ (TrkB), they...

Cyclic phosphatidic acid (cPA; 1-acyl-sn-glycerol-2,3-cyclic phosphate) is an analog of the growth factor-like phospholipid mediator lysophosphatidic (LPA). As brain tissue richest source cPA we tested its effects on hippocampal neurons from day 16/17 embryonic rat cultured in a serum-free medium. Nanomolar concentrations elicited neurotrophic effect and promoted neurite outgrowth that exceeded 50 ng/mL nerve factor (NGF). Pertussis toxin, LPA1/LPA3 receptor-selective antagonist...

Antibodies directed against nerve growth factor (NGF) immunoprecipitate a tyrosine kinase activity from NGF-treated PC12 rat pheochromocytoma cells. Based on several criteria, this has been correlated with the high-affinity and not low-affinity NGF-receptor complex. The in vitro phosphorylation of complex can be blocked by an agent that inhibits NGF (and epidermal factor)-induced cells, as well NGF-induced neuronal differentiation These observations suggest is substrate activity....

We demonstrate that the signaling adapter, Grb2, binds directly to neurotrophin receptor tyrosine kinase, TrkA. Grb2 binding TrkA is independent of Shc, FRS-2, phospholipase Cγ-1, rAPS, and SH2B observed in <i>in vitro</i> assays, yeast two-hybrid co-immunoprecipitation assays. mediated by central SH2 domain, requires a kinase-active TrkA, phosphotyrosine-dependent. By analyzing series rat mutants, we carboxyl-terminal residue, Tyr⁷⁹⁴, as well activation loop tyrosines,...

Abstract Paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents are under development for biological target identification by magnetic resonance imaging. Image associated with PARACEST can be generated radiofrequency irradiation of the chemically shifted protons bound to a agent molecule or direct on‐resonance bulk water protons. The observed signal change in image after administration is due both altered relaxation time constants and CEST effect. Despite high...