PMID- 10455108
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 35
DP  - 1999 Aug 27
TI  - Engagement of Gab1 and Gab2 in erythropoietin signaling.
PG  - 24469-74
AB  - Several signaling cascades are activated during engagement of the erythropoietin 
      receptor to mediate the biological effects of erythropoietin. The members of the 
      insulin receptor substrate (IRS) family of proteins play a central role in
      signaling for various growth factor receptors and cytokines by acting as docking 
      proteins for the SH2 domains of signaling elements, linking cytokine receptors to
      diverse downstream pathways. In the present study we provide evidence that the
      recently cloned IRS-related proteins, Gab1 and Gab2, of the Gab family of
      proteins, are rapidly phosphorylated on tyrosine during erythropoietin treatment 
      of erythropoietin-responsive cells and provide docking sites for the engagement
      of the SHP2 phosphatase and the p85 subunit of the phosphatidylinositol
      3'-kinase. Furthermore, our data show that Gab1 is the primary IRS-related
      protein activated by erythropoietin in primary erythroid progenitor cells. In
      studies to identify the erythropoietin receptor domains required for activation
      of Gab proteins, we found that tyrosines 425 and 367 in the cytoplasmic domain of
      the erythropoietin receptor are required for the phosphorylation of Gab2. Taken
      together, our data demonstrate that Gab proteins are engaged in erythropoietin
      signaling to mediate downstream activation of the SHP2 and phosphatidylinositol
      3'-kinase pathways and possibly participate in the generation of the
      erythropoietin-induced mitogenic responses.
FAU - Wickrema, A
AU  - Wickrema A
AD  - Section of Hematology-Oncology, University of Illinois at Chicago and West Side
      Veterans Affairs Medical Center, Chicago, Illinois 60607, USA. Awickrem@uic.edu
FAU - Uddin, S
AU  - Uddin S
FAU - Sharma, A
AU  - Sharma A
FAU - Chen, F
AU  - Chen F
FAU - Alsayed, Y
AU  - Alsayed Y
FAU - Ahmad, S
AU  - Ahmad S
FAU - Sawyer, S T
AU  - Sawyer ST
FAU - Krystal, G
AU  - Krystal G
FAU - Yi, T
AU  - Yi T
FAU - Nishada, K
AU  - Nishada K
FAU - Hibi, M
AU  - Hibi M
FAU - Hirano, T
AU  - Hirano T
FAU - Platanias, L C
AU  - Platanias LC
LA  - eng
GR  - CA73381/CA/NCI NIH HHS/United States
GR  - CA77816/CA/NCI NIH HHS/United States
GR  - CA79891/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (GAB1 protein, human)
RN  - 0 (GAB2 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Erythropoietin)
RN  - 11096-26-7 (Erythropoietin)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
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)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Cell Line
MH  - Erythropoietin/*metabolism
MH  - Hematopoietic Stem Cells/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Kinetics
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine/analysis
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/metabolism
MH  - Receptors, Erythropoietin/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Signal Transduction
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1074/jbc.274.35.24469 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 27;274(35):24469-74. doi: 10.1074/jbc.274.35.24469.