| RRC ID |
67306
|
| 著者 |
Walliser C, Tron K, Clauss K, Gutman O, Kobitski AY, Retlich M, Schade A, Röcker C, Henis YI, Nienhaus GU, Gierschik P.
|
| タイトル |
Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
The Rho GTPase Rac is crucially involved in controlling multiple B cell functions, including those regulated by the B cell receptor (BCR) through increased cytosolic Ca(2+). The underlying molecular mechanisms and their relevance to the functions of intact B cells have thus far remained unknown. We have previously shown that the activity of phospholipase Cγ2 (PLCγ2), a key constituent of the BCR signalosome, is stimulated by activated Rac through direct protein-protein interaction. Here, we use a Rac-resistant mutant of PLCγ2 to functionally reconstitute cultured PLCγ2-deficient DT40 B cells and to examine the effects of the Rac-PLCγ2 interaction on BCR-mediated changes of intracellular Ca(2+) and regulation of Ca(2+)-regulated and nuclear-factor-of-activated-T-cell-regulated gene transcription at the level of single, intact B cells. The results show that the functional Rac-PLCγ2 interaction causes marked increases in the following: (i) sensitivity of B cells to BCR ligation; (ii) BCR-mediated Ca(2+) release from intracellular stores; (iii) Ca(2+) entry from the extracellular compartment; and (iv) nuclear translocation of the Ca(2+)-regulated nuclear factor of activated T cells. Hence, Rac-mediated stimulation of PLCγ2 activity serves to amplify B cell receptor-induced Ca(2+) signaling.
|
| 巻・号 |
290(28)
|
| ページ |
17056-72
|
| 公開日 |
2015-7-10
|
| DOI |
10.1074/jbc.M115.645739
|
| PII |
S0021-9258(20)35311-4
|
| PMID |
25903139
|
| PMC |
PMC4498044
|
| MeSH |
Active Transport, Cell Nucleus
Amino Acid Substitution
Animals
Avian Proteins / chemistry
Avian Proteins / genetics
Avian Proteins / metabolism
B-Lymphocytes / cytology
B-Lymphocytes / immunology
B-Lymphocytes / metabolism
Calcium Signaling / physiology*
Cell Line
Chickens
Humans
Mice
Models, Molecular
Mutagenesis, Site-Directed
NFATC Transcription Factors / metabolism
Phospholipase C gamma / chemistry
Phospholipase C gamma / genetics
Phospholipase C gamma / metabolism*
Protein Conformation
Receptors, Antigen, B-Cell / metabolism*
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
rac GTP-Binding Proteins / chemistry
rac GTP-Binding Proteins / genetics
rac GTP-Binding Proteins / metabolism*
|
| IF |
4.238
|
| リソース情報 |
| ヒト・動物細胞 |
DT40(RCB1464)
PLC-γ2^(-) DT40(RCB1469) |
