PMID- 10597268
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 48
DP  - 1999 Nov 18
TI  - Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated
      protein kinase pathway.
PG  - 6635-40
AB  - The function of the pro-apoptotic molecule BAD is regulated by phosphorylation of
      two sites, serine-112 (Ser-112) and serine-136 (Ser-136). Phosphorylation at
      either site results in loss of the ability of BAD to heterodimerize with the
      survival proteins BCL-XL or BCL-2. Phosphorylated BAD binds to 14-3-3 and is
      sequestered in the cytoplasm. It has been shown that phosphorylation of BAD at
      Ser-136 is mediated by the serine/threonine protein kinase Akt-1/PKB which is
      downstream of phosphatidylinositol 3-kinase (PI3K). The signaling process leading
      to phophorylation of BAD at Ser-112 has not been identified. In this study, we
      show that phosphorylation of the two serine residues of BAD is differentially
      regulated. While Ser-136 phosphorylation is concordant with activation of Akt,
      Ser-112 phosphorylation does not correlate with Akt activation. Instead, we
      demonstrate that activated Ras and Raf, which are upstream of mitogen-activated
      protein kinases (MAPK), stimulate selective phosphorylation of BAD at Ser-112.
      Furthermore, phosphorylation of Ser-112, but not Ser-136 requires activation of
      the MAPK pathway as the MEK inhibitor, PD 98059, blocks EGF-, as well as
      activated Ras- or Raf-mediated phosphorylation of BAD at Ser-112. Therefore, the 
      PI3K-Akt and Ras-MAPK pathways converge at BAD by mediating phosphorylation of
      distinct serine residues.
FAU - Fang, X
AU  - Fang X
AD  - Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, 
      Houston 77030, USA.
FAU - Yu, S
AU  - Yu S
FAU - Eder, A
AU  - Eder A
FAU - Mao, M
AU  - Mao M
FAU - Bast, R C Jr
AU  - Bast RC Jr
FAU - Boyd, D
AU  - Boyd D
FAU - Mills, G B
AU  - Mills GB
LA  - eng
GR  - CA 64602/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (BAD protein, human)
RN  - 0 (Bad protein, mouse)
RN  - 0 (Carrier Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-Associated Death Protein)
RN  - 452VLY9402 (Serine)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Carrier Proteins/chemistry/genetics/*metabolism
MH  - Cell Line
MH  - Enzyme Activation
MH  - Gene Expression Regulation
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - Mice
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-bcl-2/chemistry/genetics/metabolism
MH  - Serine/*metabolism
MH  - bcl-Associated Death Protein
MH  - ras Proteins/*metabolism
EDAT- 1999/12/22 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/12/22 09:00
PHST- 1999/12/22 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/12/22 09:00 [entrez]
AID - 10.1038/sj.onc.1203076 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 18;18(48):6635-40. doi: 10.1038/sj.onc.1203076.