Involvement of the Gab2 scaffolding adapter in type I interferon signalling.
Interferons (IFNs) are pleiotropic cytokines involved in the regulation of physiological and pathological processes. Upon interaction with their specific receptors, IFNs activate the Jak/STAT signalling pathway. Numerous studies suggest, however, that the classical Jak/STAT pathway cannot alone account for the wide range of IFN's biological effects. To better understand the role of alternative signalling pathways in the type I IFNs response, we analyzed novel tyrosine-phosphorylated proteins following IFN-alpha2 stimulation. We showed for the first time that the Grb2-associated binder 2 (Gab2) protein is differentially phosphorylated upon the IFN subtype employed and the cells stimulated. We demonstrated that IFNAR1 physically interacts with Gab2. Moreover, the cellular content of Gab2 varies as a function of IFN receptor chain expression levels, and in particular of the ratio of IFNAR1 to IFNAR2, suggesting that Gab2 and IFNAR2 compete for interaction with IFNAR1. Analysis of Gab2 deletion mutants indicates that IFNAR1 might interact with a Gab2 region containing p85-PI3'kinase binding sites. Our results shed new light on recent data involving both Gab2 and type I IFNs in osteoclastogenesis and oncogenesis.
Baychelier
Florence
F
Laboratoire d'Oncologie virale, CNRS FRE 2937, 7 rue Guy Moquet, 94801 Villejuif, France.
Nardeux
Pierre-Claude
PC
Cajean-Feroldi
Chantal
C
Ermonval
Myriam
M
Guymarho
Jacqueline
J
Tovey
Michaël G
MG
Eid
Pierre
P
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta