title: A novel lymphocyte signaling defect: trk A mutation in the syndrome of congenital insensitivity to pain and anhidrosis (CIPA).
abstract: Congenital insensitivity to pain with anhidrosis is a syndrome characterized by loss of pain and sensation. The condition frequently evolves into deep wounds and prolonged healing times. Anhidrosis is another prominent component of the disorder. Often associated with recurrent episodes of unexplained fever, it can result in patient mortality. Recent investigations point to Trk A, the high affinity receptor for nerve growth factor (NGF), as a candidate for the site of the mutation that causes the disorder. Functional NGF receptors, such as Trk A and the Trk family of tyrosine kinases, are essential for NGF signaling of human lymphocytes. In this study, we demonstrated that the presence of a trk A mutation in patient B cells results in a novel lymphocyte signaling defect. In these B cells, NGF failed to induce Trk A phosphorylation, cytoskeleton assembly, or MAP kinase activation. These abnormalities may explain some of the clinical features of the disease.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: I
authors.initials: I
authors.lastname: Melamed
authors.forename: J
authors.initials: J
authors.lastname: Levy
authors.forename: R
authors.initials: R
authors.lastname: Parvari
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009154:Mutation; D020932:Nerve Growth Factor / Q000494:pharmacology; D010766:Phosphorylation; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*; D013577:Syndrome
chemical_list: D020932:Nerve Growth Factor; D020917:Receptor, trkA