Ubiquitin system-dependent regulation of growth hormone receptor signal transduction.
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.
Strous
G J
GJ
Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. strous@med.uu.nl
dos Santos
C Alves
CA
Gent
J
J
Govers
R
R
Sachse
M
M
Schantl
J
J
van Kerkhof
P
P
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2; D008247:Lysosomes / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000502:physiology*; D015398:Signal Transduction; D025801:Ubiquitin / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin; D025801:Ubiquitin; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2