RhoH plays critical roles in Fc epsilon RI-dependent signal transduction in mast cells.
RhoH is an atypical small G protein with defective GTPase activity that is specifically expressed in hematopoietic lineage cells. RhoH has been implicated in regulation of several physiological processes including hematopoiesis, integrin activation, and T cell differentiation and activation. In the present study, we investigated the role of RhoH in mast cells by generating RhoH knockout mice. Despite observing normal development of mast cells in vivo, passive systemic anaphylaxis and histamine release were impaired in these mice. We also observed defective degranulation and cytokine production upon FcepsilonRI ligation in RhoH-deficient bone marrow-derived mast cells. Furthermore, FcepsilonRI-dependent activation of Syk and phosphorylation of its downstream targets, including LAT, SLP76, PLCgamma1, and PLCgamma2 were impaired, however phosphorylation of the gamma-subunit of FcepsilonRI remained intact. We also found RhoH-Syk association that was greatly enhanced by active Fyn. Our results indicate that RhoH regulates FcepsilonRI signaling in mast cells by facilitating Syk activation, possibly as an adaptor molecule for Syk.
Oda
Hiroyo
H
Department of Pathology, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Fujimoto
Manabu
M
Patrick
Michael S
MS
Chida
Dai
D
Sato
Yoshinori
Y
Azuma
Yoshinao
Y
Aoki
Hiroki
H
Abe
Takaya
T
Suzuki
Harumi
H
Shirai
Mutsunori
M
D000818:Animals; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; C496930:RhoH protein, mouse; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D020741:rho GTP-Binding Proteins