Biomaterial Database

[Adult GM1 gangliosidosis--biochemical studies--1]. 1992

T Mutoh

Second Department of Internal Medicine, Fukui Medical School.

To address the pathogenesis of GM1 gangliosidosis, especially adult form, intracellular signal transduction pathway of EGF in skin fibroblasts from patients with this disorder was examined. For this purpose, skin fibroblasts from 2 different patients with adult form of the disorder and from 4 different normal controls were used. The results showed that 1) EGF-receptor autophosphorylation was diminished in skin fibroblasts from patients with altered time course of phosphorylation-dephosphorylation reaction. 2) The amount of EGF-receptor protein was decreased in cells from patients compared with that of controls. 3) 125I-EGF binding + internalization studies revealed decreased rate of EGF binding and internalization in patient cells. 4) Ribosomal S6 protein phosphorylation was strongly enhanced in naive cells from patients, but the reactivity to EGF was diminished compared with control cells. These data strongly suggest that patient fibroblasts have abnormalities in the intracellular signal transduction pathway of EGF. This paper is considered to be the first report demonstrating abnormalities in EGF-signal transducing system in human disorders.

UI	MeSH Term	Description	Entries
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D004815	Epidermal Growth Factor	A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.	EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D012867	Skin	The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016537	Gangliosidosis, GM1	An autosomal recessive neurodegenerative disorder caused by the absence or deficiency of BETA-GALACTOSIDASE. It is characterized by intralysosomal accumulation of G(M1) GANGLIOSIDE and oligosaccharides, primarily in neurons of the central nervous system. The infantile form is characterized by MUSCLE HYPOTONIA, poor psychomotor development, HIRSUTISM, hepatosplenomegaly, and facial abnormalities. The juvenile form features HYPERACUSIS; SEIZURES; and psychomotor retardation. The adult form features progressive DEMENTIA; ATAXIA; and MUSCLE SPASTICITY. (From Menkes, Textbook of Child Neurology, 5th ed, pp96-7)	G(M1) Gangliosidosis,Adult GM1 Gangliosidosis,Beta-Galactosidase-1 (GLB1) Deficiency,Beta-Galactosidase-1 Deficiency Disease,Beta-Galactosidosis,GLB1 Deficiency,GM1 Gangliosidosis,GM1-Gangliosidosis, Type I,GM1-Gangliosidosis, Type II,GM1-Gangliosidosis, Type III,Gangliosidosis G(M1),Gangliosidosis GM1,Gangliosidosis GM1 Type 3,Gangliosidosis GM1, Adult,Gangliosidosis GM1, Infantile,Gangliosidosis GM1, Juvenile,Gangliosidosis GM1, Type 1,Gangliosidosis GM1, Type 2,Gangliosidosis GM1, Type 3,Gangliosidosis Generalized GM1, Type 1,Gangliosidosis, Generalized GM1 Type 2,Gangliosidosis, Generalized GM1, Adult Type,Gangliosidosis, Generalized GM1, Chronic Type,Gangliosidosis, Generalized GM1, Infantile Form,Gangliosidosis, Generalized GM1, Juvenile Type,Gangliosidosis, Generalized GM1, Type 1,Gangliosidosis, Generalized GM1, Type 2,Gangliosidosis, Generalized GM1, Type 3,Gangliosidosis, Generalized GM1, Type I,Gangliosidosis, Generalized GM1, Type II,Gangliosidosis, Generalized GM1, Type III,Generalized Gangliosidosis,Type 3 (Adult) GM1 Gangliosidosis,beta Galactosidase 1 Deficiency,beta Galactosidase Deficiency,beta-Galactosidase Deficiency,beta-Galactosidase-1 Deficiency,Beta Galactosidase 1 Deficiency Disease,Beta Galactosidosis,Deficiencies, GLB1,Deficiency, GLB1,Deficiency, beta Galactosidase,Deficiency, beta-Galactosidase,Deficiency, beta-Galactosidase-1,GM1 Gangliosidosis, Adult,GM1 Gangliosidosis, Type I,GM1 Gangliosidosis, Type II,GM1 Gangliosidosis, Type III,GM1-Gangliosidoses, Type I,GM1-Gangliosidoses, Type II,GM1-Gangliosidoses, Type III,Gangliosidosis, Adult GM1,Infantile Gangliosidosis GM1,Juvenile Gangliosidosis GM1,Type I GM1-Gangliosidoses,Type I GM1-Gangliosidosis,Type II GM1-Gangliosidoses,Type II GM1-Gangliosidosis,Type III GM1-Gangliosidoses,Type III GM1-Gangliosidosis
D066246	ErbB Receptors	A family of structurally related cell-surface receptors that signal through an intrinsic PROTEIN-TYROSINE KINASE. The receptors are activated upon binding of specific ligands which include EPIDERMAL GROWTH FACTORS, and NEUREGULINS.	EGF Receptor,Epidermal Growth Factor Receptor,Epidermal Growth Factor Receptor Family Protein,Epidermal Growth Factor Receptor Protein-Tyrosine Kinase,ErbB Receptor,HER Family Receptor,Receptor, EGF,Receptor, Epidermal Growth Factor,Receptor, TGF-alpha,Receptor, Transforming-Growth Factor alpha,Receptor, Urogastrone,Receptors, Epidermal Growth Factor-Urogastrone,TGF-alpha Receptor,Transforming Growth Factor alpha Receptor,Urogastrone Receptor,c-erbB-1 Protein,erbB-1 Proto-Oncogene Protein,EGF Receptors,Epidermal Growth Factor Receptor Family Proteins,Epidermal Growth Factor Receptor Kinase,HER Family Receptors,Proto-oncogene c-ErbB-1 Protein,Receptor Tyrosine-protein Kinase erbB-1,Receptor, ErbB-1,Receptors, Epidermal Growth Factor,Epidermal Growth Factor Receptor Protein Tyrosine Kinase,ErbB-1 Receptor,Family Receptor, HER,Family Receptors, HER,Proto oncogene c ErbB 1 Protein,Proto-Oncogene Protein, erbB-1,Receptor Tyrosine protein Kinase erbB 1,Receptor, ErbB,Receptor, ErbB 1,Receptor, HER Family,Receptor, TGF alpha,Receptor, Transforming Growth Factor alpha,Receptors, EGF,Receptors, Epidermal Growth Factor Urogastrone,Receptors, ErbB,Receptors, HER Family,c erbB 1 Protein,c-ErbB-1 Protein, Proto-oncogene,erbB 1 Proto Oncogene Protein