[Growth hormone receptor. Structure and signal transduction].
The growth hormone receptor (GHR) belongs to the family of the prolactin and cytokine receptors. The full length receptor in a 620 amino acid protein with a unique transmembrane domain. The GH binding protein (GHBP) corresponds to the extracellular domain of the membrane GHR. In all human tissues tested, one form of 4.5 kb for the GHR mRNA was detected, suggesting that GHBP is generated through proteolytic cleavage of the membrane receptor. The three dimensional crystollographic structure of GHBP-hGH complex has identified a homodimer made of two receptor molecules and one molecule of hGH. Hormone-induced receptor dimerisation appears to be crucial for signal transduction. Functional tests using the GH effect on transcription of genes, such as SP12.1 and beta lactoglobulin, have been developed to define the sequences of the receptor which are important for signaling. A proline-rich juxtamembranous sequence, called Box 1, is important for GH effects on gene transcription, on MAP kinase activity, on cell proliferation, and on JAK2 activation. JAK2 has been identified to be a GHR-associated tyrosine kinase. The first 46 amino acids of the cytoplasmic domain are necessary for JAK2 and MAP kinase activation whereas a C-Ter sequence is necessary for the transcriptional effect. Substrates for JAK2, other than the receptor itself, have to be identified. Good candidates are the transcription factors STAT.
Postel-Vinay
M C
MC
INSERM Unité 344, Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris.
Finidori
J
J
Sotiropoulos
A
A
Dinerstein
H
H
Martini
J F
JF
Kelly
P A
PA
D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011986:Receptors, Somatotropin / Q000737:chemistry* / Q000235:genetics; D015398:Signal Transduction
D018160:Receptors, Cytoplasmic and Nuclear; D011986:Receptors, Somatotropin
Le récepteur de l'hormone de croissance. Structure et signalisation.