PMID- 7520779
OWN - NLM
STAT- MEDLINE
DCOM- 19940928
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 84
IP  - 5
DP  - 1994 Sep 1
TI  - Activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 
      receptor is dependent on protein tyrosine kinase activity.
PG  - 1579-86
AB  - Ligation of the interleukin-7 receptor (IL-7R) results in a rapid phosphorylation 
      of tyrosine residues on multiple substrates. In addition, we have recently shown 
      that the IL-7R mediates activation of phosphatidylinositol-3 (PI-3) kinase. 
      Because PI-3 kinase activity can be immunoprecipitated with antiphosphotyrosine 
      antibodies in most receptor systems studied, it has been examined that either 
      PI-3 kinase or an associated protein become tyrosine-phosphorylated after ligand 
      binding. We studied here the possibility that PI-3 kinase, which is directly 
      linked to mitogenic responses in growth factor receptors, is 
      tyrosine-phosphorylated after stimulation of the IL-7R. Using anti-p85 alpha or 
      anti-p85 beta antibodies raised against the p85 subunit of PI-3 kinase for 
      immunoprecipitation and subsequent blotting with antiphosphotyrosine clearly 
      shows that IL-7-stimulated human precursor cells contain both p85 alpha and p85 
      beta proteins phosphorylated on tyrosine residues. Specific protein tyrosine 
      kinase inhibitors such as tyrphostin AG-490 block total cell lysate 
      phosphorylation and tyrosine phosphorylation on p85. Similar concentrations of 
      this inhibitor also block in vitro and in vivo PI-3 kinase activity suggesting 
      that this enzyme activation is dependent on the phosphorylation event of p85. In 
      addition, AG-490 blocks IL-7-mediated proliferation in a dose-dependent manner, 
      suggesting a link between the early events of PI-3 kinase phosphorylation and 
      activation with IL-7R-induced cell growth.
FAU - Dadi, H
AU  - Dadi H
AD  - Division of Immunology/Allergy, University of Toronto, Hospital for Sick 
      Children, ON.
FAU - Ke, S
AU  - Ke S
FAU - Roifman, C M
AU  - Roifman CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Catechols)
RN  - 0 (Interleukin-7)
RN  - 0 (Nitriles)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tyrphostins)
RN  - 118409-60-2 (tyrphostin 47)
RN  - 21820-51-9 (Phosphotyrosine)
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 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Antigens, CD/analysis/biosynthesis
MH  - B-Lymphocytes/drug effects/immunology/*metabolism
MH  - Blotting, Western
MH  - Catechols/pharmacology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Child
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Humans
MH  - Interleukin-7/*pharmacology
MH  - Kinetics
MH  - Nitriles/pharmacology
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphoproteins/isolation & purification/metabolism
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Phosphotyrosine
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism
MH  - Receptors, Interleukin/*metabolism
MH  - Receptors, Interleukin-7
MH  - Recombinant Proteins/pharmacology
MH  - T-Lymphocytes/drug effects/immunology/*metabolism
MH  - Thymus Gland
MH  - Tumor Cells, Cultured
MH  - Tyrosine/analogs & derivatives/analysis/metabolism
MH  - *Tyrphostins
EDAT- 1994/09/01 00:00
MHDA- 1994/09/01 00:01
CRDT- 1994/09/01 00:00
PHST- 1994/09/01 00:00 [pubmed]
PHST- 1994/09/01 00:01 [medline]
PHST- 1994/09/01 00:00 [entrez]
AID - S0006-4971(20)77629-9 [pii]
PST - ppublish
SO  - Blood. 1994 Sep 1;84(5):1579-86.