PMID- 10026152
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 9
DP  - 1999 Feb 26
TI  - Oligomerization and scaffolding functions of the erythropoietin receptor
      cytoplasmic tail.
PG  - 5415-21
AB  - Signal transduction by the erythropoietin receptor (EPOR) is activated by
      ligand-mediated receptor homodimerization. However, the relationship between
      extracellular and intracellular domain oligomerization remains poorly understood.
      To assess the requirements for dimerization of receptor cytoplasmic sequences for
      signaling, we overexpressed mutant EPORs in combination with wild-type (WT) EPOR 
      to drive formation of heterodimeric (i.e. WT-mutant) receptor complexes.
      Dimerization of the membrane-proximal portion of the EPOR cytoplasmic region was 
      found to be critical for the initiation of mitogenic signaling. However,
      dimerization of the entire EPOR cytoplasmic region was not required. To examine
      this process more closely, we generated chimeras between the intracellular and
      transmembrane portions of the EPOR and the extracellular domains of the
      interleukin-2 receptor beta and gammac chains. These chimeras allowed us to
      assess more precisely the signaling role of each receptor chain because only
      heterodimers of WT and mutant receptor chimeras form in the presence of
      interleukin-2. Coexpression studies demonstrated that a functional receptor
      complex requires the membrane-proximal region of each receptor subunit in the
      oligomer to permit activation of JAK2 but only one membrane-distal tail to
      activate STAT5 and to support cell proliferation. Thus, this study defines key
      relationships involved in the assembly and activation of the EPOR signal
      transduction complex which may be applicable to other homodimeric cytokine
      receptors.
FAU - Watowich, S S
AU  - Watowich SS
AD  - Department of Immunology, M. D. Anderson Cancer Center, Houston, Texas 77030,
      USA.
FAU - Liu, K D
AU  - Liu KD
FAU - Xie, X
AU  - Xie X
FAU - Lai, S Y
AU  - Lai SY
FAU - Mikami, A
AU  - Mikami A
FAU - Longmore, G D
AU  - Longmore GD
FAU - Goldsmith, M A
AU  - Goldsmith MA
LA  - eng
GR  - CA-77447/CA/NCI NIH HHS/United States
GR  - R01 CA077447-03/CA/NCI NIH HHS/United States
GR  - R01 GM054351/GM/NIGMS NIH HHS/United States
GR  - P01 HL032262/HL/NHLBI NIH HHS/United States
GR  - GM-54351/GM/NIGMS NIH HHS/United States
GR  - R01 CA077447-02/CA/NCI NIH HHS/United States
GR  - HL32262/HL/NHLBI NIH HHS/United States
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 (Biopolymers)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Receptors, Erythropoietin)
SB  - IM
MH  - Base Sequence
MH  - Biopolymers
MH  - Cell Division
MH  - Cell Line
MH  - Cytoplasm/*metabolism
MH  - Oligodeoxyribonucleotides
MH  - Receptors, Erythropoietin/chemistry/genetics/*metabolism
MH  - Signal Transduction
PMC - PMC2388248
MID - NIHMS48569
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - 10.1074/jbc.274.9.5415 [doi]
AID - S0021-9258(19)87675-5 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Feb 26;274(9):5415-21. doi: 10.1074/jbc.274.9.5415.