Ubiquitin system-dependent regulation of growth hormone receptor signal transduction
- Resource Type
- Authors
- Gj, Strous; Ca, Dos Santos; Gent J; Roland Govers; Sachse M; Schantl J; van Kerkhof P
- Source
- Current Topics in Microbiology and Immunology
Current Topics in Microbiology and Immunology, Springer Verlag (Germany), 2004, pp.81-118
Europe PubMed Central
- Subject
- MESH : Janus Kinase 2
MESH : Cell Membrane
[ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition
[ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Endosomes
MESH : Growth Hormone
Endoplasmic Reticulum
[ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Cell Wall
Proto-Oncogene Proteins
MESH : Protein-Tyrosine Kinases
Animals
Humans
MESH : Ubiquitin
MESH : Cell Wall
MESH : Signal Transduction
MESH : Endoplasmic Reticulum
Ubiquitin
MESH : Humans
Cell Membrane
[ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
MESH : Protein Binding
Receptors, Somatotropin
MESH : Lysosomes
Janus Kinase 2
Protein-Tyrosine Kinases
MESH : Dimerization
Growth Hormone
MESH : Proto-Oncogene Proteins
MESH : Endosomes
MESH : Animals
MESH : Receptors, Somatotropin
Lysosomes
Dimerization
Protein Binding
Signal Transduction
- Language
- ISSN
- 0070-217X
International audience; The growth hormone (GH) receptor is a key regulator of cellular metabolism. Unlike most growth factor receptors, its downregulation is not initiated by its ligand. Like many growth factor receptors, specific molecular mechanisms guarantee that a receptor can signal only once in its lifetime. Three features render the GH receptor unique: (a) an active ubiquitination system is required for both uptake (endocytosis) and degradation in the lysosomes; (b) uptake of the receptor is a continuous process, independent of both GH binding and Jak2 signal transduction; (c) only the cell surface expression of dimerised GH receptors is controlled by the ubiquitin system. This system enables two independent regulatory mechanisms for the endocrinology of the GH/GHR axis: the pulsatile secretion of GH by the pituitary and the GH sensitivity of individual cells of the body by the effects of the ubiquitin system on GH receptor availability.