Role of the inositol phosphatase SHIP in B cell receptor-induced Ca2+ oscillatory response.
Src homology-2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP) is a recently identified protein that has been implicated as an important signaling molecule. Although SHIP has been shown to participate in the FcgammaRIIB-mediated inhibitory signal, the functional role of SHIP in activation responses by immunoreceptor tyrosine-based activation motif-bearing receptors such as B cell receptor (BCR) remains unclear. Indeed, it has been proposed that SHIP serves as a linking molecule for the regulation of the extracellular signal-regulated kinase pathway in BCR signaling, because SHIP associates with Shc. We now report that SHIP-deficient DT40 B cells display enhanced Ca2+ mobilization in response to BCR ligation, whereas extracellular signal-regulated kinase activation is unaffected. This Ca2+ enhancement is due to a sustained intracellular Ca2+ increase or to long-lasting Ca2+ oscillations by loss of SHIP, as revealed by single-cell Ca2+ imaging analysis. These results demonstrate the importance of SHIP in B cell activation by the modulation of Ca2+ mobilization.
Okada
H
H
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan.
Bolland
S
S
Hashimoto
A
A
Kurosaki
M
M
Kabuyama
Y
Y
Iino
M
M
Ravetch
J V
JV
Kurosaki
T
T
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D004789:Enzyme Activation / Q000276:immunology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008565:Membrane Proteins / Q000378:metabolism; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017452:Receptors, IgG / Q000502:physiology; D014162:Transfection / Q000276:immunology; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D015220:Calcium Channels; C080571:Fc gamma receptor IIB; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D017452:Receptors, IgG; C054979:antigen T cell receptor, zeta chain; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D002118:Calcium