Functional interaction of common gamma-chain and growth hormone receptor signaling apparatus

Details

Serval ID
serval:BIB_F14808A9A50D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Functional interaction of common gamma-chain and growth hormone receptor signaling apparatus
Journal
J Immunol
Author(s)
Adriani M., Garbi C., Amodio G., Russo I., Giovannini M., Amorosi S., Matrecano E., Cosentini E., Candotti F., Pignata C.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Publication state
Published
Issued date
2006
Volume
177
Number
10
Pages
6889-95
Language
english
Notes
Adriani, Marsilio
Garbi, Corrado
Amodio, Giada
Russo, Ilaria
Giovannini, Marica
Amorosi, Stefania
Matrecano, Eliana
Cosentini, Elena
Candotti, Fabio
Pignata, Claudio
eng
Research Support, Non-U.S. Gov't
J Immunol. 2006 Nov 15;177(10):6889-95.
Abstract
We previously reported on an X-linked SCID (X-SCID) patient, who also had peripheral growth hormone (GH) hyporesponsiveness and abnormalities of the protein phosphorylation events following GH receptor (GHR) stimulation. In the present study, we examined a potential role of common cytokine receptor gamma-chain (gammac) in GHR signaling using EBV-transformed lymphocytes from healthy subjects and gammac-negative X-SCID patients. We demonstrated that the proliferative response to GH stimulation of the B cell lines of gammac-negative patients was impaired despite a comparable cellular expression of GHR molecules to controls. In patients, after GH stimulation, no phosphorylation of STAT5 was observed. In addition, the molecule localization through confocal microscopy revealed that in B cell lines of patients no nuclear translocation of STAT5b following GH stimulation occurred differently from controls. Biochemical analysis of the nuclear extracts of gammac-negative cell lines provided further evidence that the amount of STAT5b and its phosphorylated form did not increase following GH stimulation. In patients, cells reconstituted with wild-type gammac abnormal biochemical and functional events were restored resulting in nuclear translocation of STAT5. Confocal experiments revealed that GHR and gammac were colocalized on the cell membrane. Our study demonstrates the existence of a previously unappreciated relationship between GHR-signaling pathway and gammac, which is required for the activation of STAT5b in B cell lines. These data also confirm that growth failure in X-SCID is primarily related to the genetic alteration of the IL2RG gene.
Keywords
Active Transport, Cell Nucleus/genetics, Cell Line, Cell Line, Transformed, Cell Membrane/immunology/metabolism, Cell Nucleus/genetics/metabolism, Cell Proliferation, Cell Transformation, Viral/genetics, Cells, Cultured, Chromosomes, Human, X/genetics, Genetic Linkage, Herpesvirus 4, Human/genetics, Humans, Interleukin Receptor Common gamma Subunit/deficiency/genetics/*physiology, Phosphorylation, Receptors, Somatotropin/*physiology, STAT5 Transcription Factor/genetics/metabolism, Severe Combined Immunodeficiency/genetics/immunology/*metabolism, *Signal Transduction/genetics/immunology, Tyrosine/metabolism
Pubmed
Create date
01/11/2017 11:29
Last modification date
20/08/2019 17:18
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