PMID- 19509406
OWN - NLM
STAT- MEDLINE
DCOM- 20090806
LR  - 20160513
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 2
IP  - 74
DP  - 2009 Jun 9
TI  - PI3Kgamma adaptor subunits define coupling to degranulation and cell motility by 
      distinct PtdIns(3,4,5)P3 pools in mast cells.
PG  - ra27
LID - 10.1126/scisignal.2000259 [doi]
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) plays a major role in chronic 
      inflammation and allergy. It is a heterodimer of a catalytic p110gamma subunit 
      and an adaptor protein, either p101 or the p101 homolog p84 (p87(PIKAP)). It is 
      unclear whether both PI3Kgamma complexes specifically modulate responses such as 
      chemotaxis and degranulation. In mast cells, the p84:p110gamma complex synergizes 
      with immunoglobulin E (IgE)- and antigen-clustered FcepsilonRI receptor signaling 
      and is required to achieve maximal degranulation. During this process, PI3Kgamma 
      is activated by ligands of heterotrimeric guanine nucleotide-binding protein (G 
      protein)-coupled receptors (GPCRs), in particular adenosine receptors, through 
      autocrine and paracrine pathways. Here, we show that p110gamma needs p84 to relay 
      signals from GPCRs to formation of phosphatidylinositol 3,4,5-trisphosphate 
      [PtdIns(3,4,5)P(3)], phosphorylation of Akt, migration of cells, and synergistic 
      adenosine-enforced degranulation. Furthermore, the absence of adaptor subunits 
      could not be compensated for by increased p110gamma abundance. Differentiated, 
      p110gamma null cells also lost adaptor proteins. Complementation of p110gamma 
      null mast cells with p101 and p110gamma restored the activation of Akt and cell 
      migration, but failed to support degranulation. Lack of degranulation was 
      attributed to a change in the spatiotemporal localization of PI3Kgamma-derived 
      PtdIns(3,4,5)P(3); although both p84:p110gamma and p101:p110gamma complexes 
      initially deposited PtdIns(3,4,5)P(3) at the plasma membrane, 
      p101:p110gamma-derived PtdIns(3,4,5)P(3) was rapidly endocytosed to motile, 
      microtubule-associated vesicles. In addition, p84:p110gamma, but not 
      p101:p110gamma signaling was sensitive to disruption of lipid rafts. Our results 
      demonstrate a nonredundant function for the p101 and p84 PI3Kgamma adaptor 
      proteins and show that distinct pools of PtdIns(3,4,5)P(3) at the plasma membrane 
      can elicit specific cell responses.
FAU - Bohnacker, Thomas
AU  - Bohnacker T
AD  - Institute of Biochemistry and Genetics, Department of Biomedicine, University of 
      Basel, Mattenstrasse 28, Basel, Switzerland.
FAU - Marone, Romina
AU  - Marone R
FAU - Collmann, Emilie
AU  - Collmann E
FAU - Calvez, Ronan
AU  - Calvez R
FAU - Hirsch, Emilio
AU  - Hirsch E
FAU - Wymann, Matthias P
AU  - Wymann MP
LA  - eng
PT  - Journal Article
DEP - 20090609
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Potassium Channels)
RN  - 0 (Protein Subunits)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 147205-48-9 (AKT1 protein, Arabidopsis)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class Ib Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.137 (PIK3CG protein, human)
RN  - EC 2.7.1.153 (Pik3cg protein, mouse)
SB  - IM
CIN - Sci Signal. 2009;2(74):pe35. PMID: 19509404
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Animals
MH  - Arabidopsis Proteins/metabolism
MH  - Bone Marrow Cells/physiology
MH  - *Cell Degranulation
MH  - Cell Membrane/metabolism
MH  - *Cell Movement
MH  - Cells, Cultured
MH  - Class Ib Phosphatidylinositol 3-Kinase
MH  - Humans
MH  - Isoenzymes/physiology
MH  - Mast Cells/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multiprotein Complexes/physiology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphatidylinositol 4,5-Diphosphate/metabolism
MH  - Phosphatidylinositol Phosphates/metabolism
MH  - Potassium Channels/metabolism
MH  - Protein Subunits/physiology
MH  - Rats
MH  - Signal Transduction
EDAT- 2009/06/11 09:00
MHDA- 2009/08/07 09:00
CRDT- 2009/06/11 09:00
PHST- 2009/06/11 09:00 [entrez]
PHST- 2009/06/11 09:00 [pubmed]
PHST- 2009/08/07 09:00 [medline]
AID - 2/74/ra27 [pii]
AID - 10.1126/scisignal.2000259 [doi]
PST - epublish
SO  - Sci Signal. 2009 Jun 9;2(74):ra27. doi: 10.1126/scisignal.2000259.