PMID- 10438924
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20161124
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 4
DP  - 1999 Aug 15
TI  - The B cell antigen receptor activates the Akt (protein kinase B)/glycogen
      synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase.
PG  - 1894-905
AB  - We have previously shown that the B cell Ag receptor (BCR) activates
      phosphatidylinositol (PI) 3-kinase. We now show that a serine/threonine kinase
      called Akt or protein kinase B is a downstream target of PI 3-kinase in B cells. 
      Akt has been shown to promote cell survival as well as the transcription and
      translation of proteins involved in cell cycle progression. Using an Ab that
      specifically recognizes the activated form of Akt that is phosphorylated on
      serine 473, we show that BCR engagement activates Akt in a PI 3-kinase-dependent 
      manner. These results were confirmed using in vitro kinase assays. Moreover, BCR 
      ligation also induced phosphorylation of Akt of threonine 308, another
      modification that is required for activation of Akt. In the DT40 chicken B cell
      line, phosphorylation of Akt on serine 473 was completely dependent on the Lyn
      tyrosine kinase, while the Syk tyrosine kinase was required for sustained
      phosphorylation of Akt. Complementary experiments in BCR-expressing AtT20
      endocrine cells confirmed that Src kinases are sufficient for BCR-induced Akt
      phosphorylation, but that Syk is required for sustained phosphorylation of Akt on
      both serine 473 and threonine 308. In insulin-responsive cells, Akt
      phosphorylates and inactivates the serine/threonine kinase glycogen synthase
      kinase-3 (GSK-3). Inactivation of GSK-3 may promote nuclear accumulation of
      several transcription factors, including NF-ATc. We found that BCR engagement
      induced GSK-3 phosphorylation and decreased GSK-3 enzyme activity. Thus, BCR
      ligation initiates a PI 3-kinase/Akt/GSK-3 signaling pathway.
FAU - Gold, M R
AU  - Gold MR
AD  - Department of Microbiology and Immunology, University of British Columbia,
      Vancouver, Canada. mgold@unixg.ubc.ca
FAU - Scheid, M P
AU  - Scheid MP
FAU - Santos, L
AU  - Santos L
FAU - Dang-Lawson, M
AU  - Dang-Lawson M
FAU - Roth, R A
AU  - Roth RA
FAU - Matsuuchi, L
AU  - Matsuuchi L
FAU - Duronio, V
AU  - Duronio V
FAU - Krebs, D L
AU  - Krebs DL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Enzyme Precursors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (Syk protein, mouse)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.- (Glycogen Synthase Kinases)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Line
MH  - Enzyme Activation/immunology
MH  - Enzyme Precursors/physiology
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - *Protein-Serine-Threonine Kinases
MH  - Protein-Tyrosine Kinases/physiology
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptors, Antigen, B-Cell/immunology/metabolism/*physiology
MH  - Serine/metabolism
MH  - Signal Transduction/*immunology
MH  - Syk Kinase
MH  - Threonine/metabolism
MH  - Tumor Cells, Cultured
MH  - src-Family Kinases/physiology
EDAT- 1999/08/10 00:00
MHDA- 1999/08/10 00:01
CRDT- 1999/08/10 00:00
PHST- 1999/08/10 00:00 [pubmed]
PHST- 1999/08/10 00:01 [medline]
PHST- 1999/08/10 00:00 [entrez]
AID - ji_v163n4p1894 [pii]
PST - ppublish
SO  - J Immunol. 1999 Aug 15;163(4):1894-905.