PMID- 10385529
OWN - NLM
STAT- MEDLINE
DCOM- 19990802
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 145
IP  - 7
DP  - 1999 Jun 28
TI  - The dynamics of protein kinase B regulation during B cell antigen receptor
      engagement.
PG  - 1511-20
AB  - This study has used biochemistry and real time confocal imaging of green
      fluorescent protein (GFP)-tagged molecules in live cells to explore the dynamics 
      of protein kinase B (PKB) regulation during B lymphocyte activation. The data
      show that triggering of the B cell antigen receptor (BCR) induces a transient
      membrane localization of PKB but a sustained activation of the enzyme; active PKB
      is found in the cytosol and nuclei of activated B cells. Hence, PKB has three
      potential sites of action in B lymphocytes; transiently after BCR triggering PKB 
      can phosphorylate plasma membrane localized targets, whereas during the sustained
      B cell response to antigen, PKB acts in the nucleus and the cytosol. Membrane
      translocation of PKB and subsequent PKB activation are dependent on BCR
      activation of phosphatidylinositol 3-kinase (PI3K). Moreover, PI3K signals are
      both necessary and sufficient for sustained activation of PKB in B lymphocytes.
      However, under conditions of continuous PI3K activation or BCR triggering there
      is only transient recruitment of PKB to the plasma membrane, indicating that
      there must be a molecular mechanism to dissociate PKB from sites of PI3K activity
      in B cells. The inhibitory Fc receptor, the FcgammaRIIB, mediates vital
      homeostatic control of B cell function by recruiting an inositol 5 phosphatase
      SHIP into the BCR complex. Herein we show that coligation of the BCR with the
      inhibitory FcgammaRIIB prevents membrane targeting of PKB. The FcgammaRIIB can
      thus antagonize BCR signals for PKB localization and prevent BCR stimulation of
      PKB activity which demonstrates the mechanism for the inhibitory action of the
      FcgammaRIIB on the BCR/PKB response.
FAU - Astoul, E
AU  - Astoul E
AD  - Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX,
      United Kingdom.
FAU - Watton, S
AU  - Watton S
FAU - Cantrell, D
AU  - Cantrell D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Antigens, CD)
RN  - 0 (Fc gamma receptor IIB)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 0 (Receptors, IgG)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
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)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.86 (INPPL1 protein, human)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - B-Lymphocytes/cytology/drug effects/*enzymology/immunology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Membrane/drug effects/enzymology/metabolism
MH  - Cell Nucleus/drug effects/enzymology/metabolism
MH  - Cytosol/drug effects/enzymology/metabolism
MH  - Enzyme Activation/drug effects
MH  - Glycogen Synthase Kinase 3
MH  - Immunoglobulin Fab Fragments/immunology/pharmacology
MH  - Immunoglobulin G/immunology/pharmacology
MH  - *Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microscopy, Confocal
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
MH  - Phosphoric Monoester Hydrolases/metabolism
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/analysis/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptor Aggregation/drug effects
MH  - Receptors, Antigen, B-Cell/antagonists & inhibitors/*immunology
MH  - Receptors, IgG/metabolism
MH  - Recombinant Fusion Proteins/analysis/biosynthesis/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC2133167
EDAT- 1999/06/29 00:00
MHDA- 1999/06/29 00:01
CRDT- 1999/06/29 00:00
PHST- 1999/06/29 00:00 [pubmed]
PHST- 1999/06/29 00:01 [medline]
PHST- 1999/06/29 00:00 [entrez]
AID - 10.1083/jcb.145.7.1511 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Jun 28;145(7):1511-20. doi: 10.1083/jcb.145.7.1511.