Role of GTP binding, isoprenylation, and the C-terminal α-helices in the inhibition of cell spreading by the interferon-induced GTPase, mouse guanylate-binding protein-2.
J Interferon Cytokine Res
; 31(3): 291-8, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-20950129
ABSTRACT
Interferon-γ pre-exposure inhibits Rac activation by either integrin engagement or platelet-derived growth factor treatment. Interferon-γ does this by inducing expression of the large guanosine triphosphatase (GTPase) mouse guanylate-binding protein (mGBP-2). Inhibiting Rac results in the retardation of cell spreading. Analysis of variants of mGBP-2 containing amino acid substitutions in the guanosine triphosphate (GTP) binding domain suggests that GTP binding, and possibly dimerization, of mGBP-2 is necessary to inhibit cell spreading. However, isoprenylation is also required. Removal of the N-terminal GTP-binding globular domain from mGBP-2 yields a protein with only the extended C-terminal α-helices that lacks enzymatic activity. The ability of the C-terminal α-helices alone to inhibit cell spreading suggests that this is the domain that interacts with the downstream effectors of mGBP-2. Interestingly, mGBP-2 can inhibit cell spreading whether it is geranylgeranylated or farnesylated. This study begins to define the properties of mGBP-2 responsible for inhibiting cell spreading.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Prenilação de Proteína
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Proteínas de Ligação ao GTP
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Proteínas rac de Ligação ao GTP
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Guanosina Trifosfato
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article