Metalloproteinases and the modulation of GH signaling.
J Endocrinol
; 174(3): 361-8, 2002 Sep.
Article
en En
| MEDLINE
| ID: mdl-12208655
ABSTRACT
The metzincin metalloproteinase, tumor necrosis factor-alpha-converting enzyme (TACE), also known as ADAM (a disintegrin and metalloproteinase) 17, has recently been identified as an important enzyme for cleavage of the GH receptor (GHR) and shedding of GH-binding protein (GHBP). Proteolysis can be induced by phorbol esters, platelet-derived growth factor and serum; it is dependent on protein kinase C and partially on MAP kinase pathways. Proteolysis occurs at the cell surface, leading to extracellular release of GHBP and intracellular GHR remnant accumulation. The GHR remnant is further processed by gamma-secretase activity, possibly leading to biologically active products. TACE-dependent GHR proteolysis can be inhibited by GH as the dimerized GHR is resistant to cleavage. The cleavage site lies within a short juxtamembranous stem region that extends between the transmembrane helix and the globular dimerization domain of the GHR. GHR proteolysis leads to downregulation of functional GHRs at the cell surface, and has complex secondary effects on GH action via GHBP and GHR remnant generation.
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Base de datos:
MEDLINE
Asunto principal:
Péptido Hidrolasas
/
Hormona del Crecimiento
/
Metaloendopeptidasas
/
Transducción de Señal
/
Fenómenos Fisiológicos Celulares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Endocrinol
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos