Phosphatidylinositol 3'-kinase and SH2-containing inositol phosphatase (SHIP) are recruited by distinct positive and negative growth-regulatory domains in the granulocyte colony-stimulating factor receptor.
J Immunol
; 160(10): 4979-87, 1998 May 15.
Article
en En
| MEDLINE
| ID: mdl-9590246
Activation of both positive and "negative" or anti-proliferative signals has emerged as a common paradigm for regulation of cell growth through cell surface receptors that regulate immune responses. SHP-1 and -2 and the novel 5'-inositol phosphatase SHIP have recently been shown to function as growth inhibitory molecules in immune receptor signaling. In the current study, we have identified distinct regions in the granulocyte colony-stimulating factor receptor (G-CSFR) distal to the conserved box 2 motif necessary for mitogenesis, which exert positive and negative influences on growth signaling in Ba/F3 pro-B lymphoid cells. The region spanning amino acids 682 to 715 mediates activation of phosphatidylinositol 3'(PI3)-kinase. Activation of PI3-kinase leads to inhibition of apoptosis, promotion of cell survival, and enhanced proliferative responses to G-CSF. We show that the region of 98 amino acids in the distal tail of the class I G-CSFR down-modulates proliferative signaling, not only in myeloid cell lines, as previously reported, but also in Ba/F3 cells. This same region recruits SHIP to the signaling cascade through a mechanism involving Shc, with the formation of Shc/SHIP complexes. Our data suggest a model in which PI3-kinase and SHIP coordinately regulate growth signaling through the G-CSFR.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
División Celular
/
Proteínas Tirosina Fosfatasas
/
Receptores de Factor Estimulante de Colonias de Granulocito
/
Fosfatidilinositol 3-Quinasas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos