PMID- 8086421
OWN - NLM
STAT- MEDLINE
DCOM- 19941018
LR  - 20190613
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 33
IP  - 36
DP  - 1994 Sep 13
TI  - Tyrosine 508 of the 85-kilodalton subunit of phosphatidylinositol 3-kinase is 
      phosphorylated by the platelet-derived growth factor receptor.
PG  - 11046-50
AB  - The mechanisms by which growth factors and oncogenic agents activate 
      phosphatidylinositol 3-kinase (PI3 kinase) are unknown. Previously, we reported 
      that the 85-kDa regulatory subunit of PI3 kinase is tyrosine-phosphorylated both 
      in vitro by the platelet-derived growth factor beta-receptor (PDGFR) tyrosine 
      kinase and in fibroblasts in response to PDGF. As a first step in determining the 
      role of tyrosine phosphorylation in PDGF signaling through PI3 kinase, we 
      investigated which tyrosines on p85 are phosphorylated by the PDGFR. Recombinant 
      p85 was phosphorylated with recombinant PDGF receptors, and tryptic 
      phosphopeptides were purified by HPLC and analyzed by Edman degradation. By this 
      approach and by mutational analysis, Y508 was identified as the major in vitro 
      phosphorylation site. Tryptic phosphopeptide mapping demonstrated Y508 to also be 
      phosphorylated in vivo in COS cells. Comparison of these data with a previous 
      report [Hayashi, H., Nishioka, Y., Kamohara, S., Kanai, F., Ishii, K., Fukui, Y., 
      Shibasaki, F., Takenawa, T., Kido, H., Katsunuma, N., & Ebina, Y. (1993) J. Biol. 
      Chem. 268, 7107-7117] suggests that p85 is phosphorylated differently by the PDGF 
      and insulin receptor tyrosine kinases. Therefore, p85 may be regulated 
      differently by PDGF and insulin. Mapping of phosphorylation sites on p85 may lead 
      to new insights into the regulation of signal transduction through PI3 kinase.
FAU - Kavanaugh, W M
AU  - Kavanaugh WM
AD  - Department of Medicine, University of California, San Francisco 94143.
FAU - Turck, C W
AU  - Turck CW
FAU - Klippel, A
AU  - Klippel A
FAU - Williams, L T
AU  - Williams LT
LA  - eng
GR  - K11 HL02410/HL/NHLBI NIH HHS/United States
GR  - R01 HL32898/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Recombinant Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Chromatography, High Pressure Liquid
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Mice
MH  - Molecular Sequence Data
MH  - Peptide Mapping
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/chemistry/*metabolism
MH  - Receptors, Platelet-Derived Growth Factor/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Tyrosine/*metabolism
EDAT- 1994/09/13 00:00
MHDA- 1994/09/13 00:01
CRDT- 1994/09/13 00:00
PHST- 1994/09/13 00:00 [pubmed]
PHST- 1994/09/13 00:01 [medline]
PHST- 1994/09/13 00:00 [entrez]
AID - 10.1021/bi00202a026 [doi]
PST - ppublish
SO  - Biochemistry. 1994 Sep 13;33(36):11046-50. doi: 10.1021/bi00202a026.