| RRC ID |
73231
|
| 著者 |
Blois JT, Mataraza JM, Mecklenbraüker I, Tarakhovsky A, Chiles TC.
|
| タイトル |
B cell receptor-induced cAMP-response element-binding protein activation in B lymphocytes requires novel protein kinase Cdelta.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
The cAMP-response element-binding protein (CREB) is activated by phosphorylation on Ser-133 and plays a key role in the proliferative and survival responses of mature B cells to B cell receptor (BCR) signaling. The signal link between the BCR and CREB activation depends on a phorbol ester (phorbol 12-myristate 13-acetate)-sensitive protein kinase C (PKC) activity and not protein kinase A or calmodulin kinase; however, the identity and role of the PKC(s) activity has not been elucidated. We found the novel PKCdelta (nPKCdelta) activator bistratene A is sufficient to induce CREB phosphorylation in murine splenic B cells. The pharmacological inhibitor Gö6976, which targets conventional PKCs and PKCmu, has no effect on CREB phosphorylation, whereas the nPKCdelta inhibitor rottlerin blocks CREB phosphorylation following BCR cross-linking. Bryostatin 1 selectively prevents nPKCdelta depletion by phorbol 12-myristate 13-acetate when coapplied, coincident with protection of BCR-induced CREB phosphorylation. Ectopic expression of a kinase-inactive nPKCdelta blocks BCR-induced CREB phosphorylation in A20 B cells. In addition, BCR-induced CREB phosphorylation is significantly diminished in nPKCdelta-deficient splenic B cells in comparison with wild type mice. Consistent with the essential role for Bruton's tyrosine kinase and phospholipase Cgamma2 in mediating PKC activation, Bruton's tyrosine kinase- and phospholipase Cgamma2-deficient B cells display defective CREB phosphorylation by the BCR. We also found that p90 RSK directly phosphorylates CREB on Ser-133 following BCR cross-linking and is positioned downstream of nPKCdelta. Taken together, these results suggest a model in which BCR engagement leads to the phosphorylation of CREB via a signaling pathway that requires nPKCdelta and p90 RSK in mature B cells.
|
| 巻・号 |
279(29)
|
| ページ |
30123-32
|
| 公開日 |
2004-7-16
|
| DOI |
10.1074/jbc.M402793200
|
| PII |
S0021-9258(19)71024-2
|
| PMID |
15138267
|
| MeSH |
Acetamides / pharmacology
Acetophenones / pharmacology
Animals
B-Lymphocytes / metabolism*
Benzopyrans / pharmacology
Binding Sites
Blotting, Western
Bryostatins
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
Carbazoles / pharmacology
Cell Division
Cross-Linking Reagents / pharmacology
Cyclic AMP Response Element-Binding Protein / metabolism*
Cyclic AMP-Dependent Protein Kinases / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Indoles / pharmacology
Lactones / pharmacology
Macrolides
Mice
Mice, Inbred BALB C
Mice, Inbred CBA
Mitogens
Phosphorylation
Promoter Regions, Genetic
Protein Isoforms
Protein Kinase C / metabolism*
Protein Kinase C-delta
Protein Structure, Tertiary
Pyrans / pharmacology
Receptors, Antigen, B-Cell / metabolism*
Ribosomal Protein S6 Kinases, 90-kDa / metabolism
Serine / chemistry
Signal Transduction
Spiro Compounds / pharmacology
Tetradecanoylphorbol Acetate
Time Factors
|
| IF |
4.238
|
| リソース情報 |
| ヒト・動物細胞 |
PLC-γ2^(-) DT40(RCB1469)
Btk^(-) DT40(RCB1468)
Syk^(-) DT40(RCB1470) |
