Requirement of Gab2 for mast cell development and KitL/c-Kit signaling.
Mast cells are thought to participate in a variety of immune responses, such as parasite resistance and the allergic reaction. Mast cell development depends on stem cell factor (Kit ligand) and its receptor, c-Kit. Gab2 is an adaptor molecule containing a pleckstrin homology domain and potential binding sites for SH2 and SH3 domains. Gab2 is phosphorylated on tyrosine after stimulation with cytokines and growth factors, including KitL. Gab2-deficient mice were created to define the physiological requirement for Gab2 in KitL/c-Kit signaling and mast cell development. In Gab2-deficient mice, the number of mast cells was reduced markedly in the stomach and less severely in the skin. Bone marrow-derived mast cells (BMMCs) from the Gab2-deficient mice grew poorly in response to KitL. KitL-induced ERK MAP kinase and Akt activation were impaired in Gab2-deficient BMMCs. These data indicate that Gab2 is required for mast cell development and KitL/c-Kit signaling.
Nishida
Keigo
K
Department of Molecular Oncology (C-7), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Wang
Lin
L
Morii
Eiichi
E
Park
Sung Joo
SJ
Narimatsu
Masahiro
M
Itoh
Shousaku
S
Yamasaki
Satoru
S
Fujishima
Masahiro
M
Ishihara
Katsuhiko
K
Hibi
Masahiko
M
Kitamura
Yukihiko
Y
Hirano
Toshio
T
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology; D019089:Stem Cell Factor / Q000502:physiology; D013270:Stomach / Q000166:cytology
D048868:Adaptor Proteins, Signal Transducing; C490894:Gab2 protein, mouse; D010750:Phosphoproteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit