PMID- 10194437
OWN - NLM
STAT- MEDLINE
DCOM- 19990503
LR  - 20161124
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 8
DP  - 1999 Apr 15
TI  - Erythropoietin induces the tyrosine phosphorylation of GAB1 and its association
      with SHC, SHP2, SHIP, and phosphatidylinositol 3-kinase.
PG  - 2578-85
AB  - Five tyrosine-phosphorylated proteins with molecular masses of 180, 145, 116,
      100, and 70 kD are associated with phosphatidylinositol 3-kinase (PI 3-kinase) in
      erythropoietin (Epo)-stimulated UT-7 cells. The 180- and 70-kD proteins have been
      previously shown to be IRS2 and the Epo receptor. In this report, we show that
      the 116-kD protein is the IRS2-related molecular adapter, GAB1. Indeed, Epo
      induced the transient tyrosine phosphorylation of GAB1 in UT-7 cells. Both
      kinetics and Epo dose-response experiments showed that GAB1 tyrosine
      phosphorylation was a direct consequence of Epo receptor activation. After
      tyrosine phosphorylation, GAB1 associated with the PI 3-kinase, the
      phosphotyrosine phosphatase SHP2, the phosphatidylinositol 3,4,5 trisphosphate
      5-phosphatase SHIP, and the molecular adapter SHC. GAB1 was also associated with 
      the molecular adapter GRB2 in unstimulated cells, and this association
      dramatically increased after Epo stimulation. Thus, GAB1 could be a scaffold
      protein able to couple the Epo receptor activation with the stimulation of
      several intracellular signaling pathways. Epo-induced tyrosine phosphorylation of
      GAB1 was also observed in normal human erythroid progenitors isolated from cord
      blood. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      thrombopoietin (TPO) also induced the tyrosine phosphorylation of GAB1 in UT-7
      cells, indicating that this molecule participates in the signal transduction of
      several cytokine receptors.
FAU - Lecoq-Lafon, C
AU  - Lecoq-Lafon C
AD  - Institut Cochin de Genetique Moleculaire (ICGM), Institut National de la Sante et
      de la Recherche Medicale (INSERM U363), France.
FAU - Verdier, F
AU  - Verdier F
FAU - Fichelson, S
AU  - Fichelson S
FAU - Chretien, S
AU  - Chretien S
FAU - Gisselbrecht, S
AU  - Gisselbrecht S
FAU - Lacombe, C
AU  - Lacombe C
FAU - Mayeux, P
AU  - Mayeux P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (GAB1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SHC1 protein, human)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - 0 (Src Homology 2 Domain-Containing, Transforming Protein 1)
RN  - 11096-26-7 (Erythropoietin)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.48 (PTPN11 protein, human)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (SH2 Domain-Containing Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.86 (INPPL1 protein, human)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
SB  - AIM
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence
MH  - Erythropoietin/*pharmacology
MH  - Fetal Blood
MH  - Hematopoietic Stem Cells/cytology/drug effects/*physiology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Leukemia
MH  - Molecular Weight
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
MH  - Phosphoproteins/*metabolism
MH  - Phosphoric Monoester Hydrolases/*metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Proteins/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - SH2 Domain-Containing Protein Tyrosine Phosphatases
MH  - Shc Signaling Adaptor Proteins
MH  - Src Homology 2 Domain-Containing, Transforming Protein 1
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - src Homology Domains
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Apr 15;93(8):2578-85.