PMID- 10611223
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20191210
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 2
DP  - 2000 Jan
TI  - p21-activated kinase 1 phosphorylates the death agonist bad and protects cells
      from apoptosis.
PG  - 453-61
AB  - Bad is a critical regulatory component of the intrinsic cell death machinery that
      exerts its death-promoting effect upon heterodimerization with the antiapoptotic 
      proteins Bcl-2 and Bcl-x(L). Growth factors promote cell survival through
      phosphorylation of Bad, resulting in its dissociation from Bcl-2 and Bcl-x(L) and
      its association with 14-3-3tau. Survival of interleukin 3 (IL-3)-dependent FL5.12
      lymphoid progenitor cells is attenuated upon treatment with the Rho
      GTPase-inactivating toxin B from Clostridium difficile. p21-activated kinase 1
      (PAK1) is activated by IL-3 in FL5.12 cells, and this activation is reduced by
      the phosphatidylinositol 3-kinase inhibitor LY294002. Overexpression of a
      constitutively active PAK mutant (PAK1-T423E) promoted cell survival of FL5.12
      and NIH 3T3 cells, while overexpression of the autoinhibitory domain of PAK
      (amino acids 83 to 149) enhanced apoptosis. PAK phosphorylates Bad in vitro and
      in vivo on Ser112 and Ser136, resulting in a markedly reduced interaction between
      Bad and Bcl-2 or Bcl-x(L) and the increased association of Bad with 14-3-3tau.
      Our findings indicate that PAK inhibits the proapoptotic effects of Bad by direct
      phosphorylation and that PAK may play an important role in cell survival
      pathways.
FAU - Schurmann, A
AU  - Schurmann A
AD  - Institut fur Pharmakologie und Toxikologie, Medizinische Fakulat,
      Rheinisch-Westfalische Technische Hochschule Aachen, D52057 Aachen, Germany.
FAU - Mooney, A F
AU  - Mooney AF
FAU - Sanders, L C
AU  - Sanders LC
FAU - Sells, M A
AU  - Sells MA
FAU - Wang, H G
AU  - Wang HG
FAU - Reed, J C
AU  - Reed JC
FAU - Bokoch, G M
AU  - Bokoch GM
LA  - eng
GR  - P01 CA069381/CA/NCI NIH HHS/United States
GR  - R01 AG015430/AG/NIA NIH HHS/United States
GR  - AG15430/AG/NIA NIH HHS/United States
GR  - CA-69381/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Bad protein, mouse)
RN  - 0 (Bcl2l1 protein, mouse)
RN  - 0 (Carrier Proteins)
RN  - 0 (Interleukin-3)
RN  - 0 (N-acetylsphingosine)
RN  - 0 (Peptide Fragments)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-Associated Death Protein)
RN  - 0 (bcl-X Protein)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.11.1 (Pak1 protein, mouse)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - 14-3-3 Proteins
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Carrier Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Enzyme Activation/drug effects
MH  - Interleukin-3/pharmacology
MH  - Mice
MH  - Mutation/genetics
MH  - Peptide Fragments/chemistry/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Protein Binding
MH  - Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Signal Transduction/drug effects
MH  - Sphingosine/analogs & derivatives/pharmacology
MH  - *Tyrosine 3-Monooxygenase
MH  - bcl-Associated Death Protein
MH  - bcl-X Protein
MH  - cdc42 GTP-Binding Protein/metabolism
MH  - p21-Activated Kinases
MH  - rho GTP-Binding Proteins/antagonists & inhibitors/metabolism
PMC - PMC85099
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - 10.1128/mcb.20.2.453-461.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Jan;20(2):453-61. doi: 10.1128/mcb.20.2.453-461.2000.