Recycling of cell surface pro-transforming growth factor-{alpha} regulates epidermal growth factor receptor activation. 2005

Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
Medical Oncology Research Program, Vall d'Hebron Research Institute University Hospital, 119-129 Psg. Vall d'Hebron, Barcelona 08035, Spain.

Impairments in signal transduction, leading to the regulation of cell proliferation, differentiation, or migration are frequently the cause of cancer. Since the accurate spatial and temporal location of their components is crucial to ensure the correct regulation of these signaling pathways, it could be anticipated that defects in intracellular trafficking are at the base of certain neoplasias. However, the trafficking of many components of pathways frequently up-regulated in cancers, such as the epidermal growth factor receptor (EGFR) pathway, are largely unknown. Here, we show that the pro-transforming growth factor-alpha (pro-TGF-alpha), a prototypical EGFR ligand, is endocytosed from the cell surface via a clathrin-dependent pathway. Internalized pro-TGF-alpha does not progress to the lysosome; instead, it is delivered to the cell surface via recycling endosomes. To analyze the functional meaning of the internalization of pro-TGF-alpha, we used a deletion construct that is normally transported to the cell surface but is deficiently endocytosed. Due to this impairment, the levels of this construct at the cell surface are dramatically augmented. Consequently, the deletion construct displays a higher EGFR-activating ability, revealing a link between the trafficking of pro-TGF-alpha and the signaling by the EGFR and opening the possibility that defects in the trafficking of the growth factor may contribute to the development of tumors.

UI MeSH Term Description Entries
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D011498 Protein Precursors Precursors, Protein
D011992 Endosomes Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Receptosomes,Endosome,Receptosome
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002966 Clathrin The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster

Related Publications

Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
July 1990, Cancer research,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
July 1989, Biochemistry,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
January 1992, In vivo (Athens, Greece),
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
January 1990, Biochemical and biophysical research communications,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
March 2009, Molecular biology of the cell,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
June 1994, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
April 1989, British medical bulletin,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
December 1991, Bailliere's clinical endocrinology and metabolism,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
January 1996, Journal of cancer research and clinical oncology,
Sonia Martínez-Arca, and Joan Josep Bech-Serra, and Miguel Hurtado-Küttner, and Aldo Borroto, and Joaquín Arribas
October 1992, Biochemistry,
Copied contents to your clipboard!