PMID- 10477686
OWN - NLM
STAT- MEDLINE
DCOM- 19990929
LR  - 20061115
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 5
DP  - 1999 Sep 1
TI  - Heterodimerization of the alpha and beta chains of the interleukin-3 (IL-3)
      receptor is necessary and sufficient for IL-3-induced mitogenesis.
PG  - 1614-22
AB  - The high-affinity receptor for interleukin-3 (IL-3) is a complex of the
      IL-3-binding subunit (alpha(IL-3)) and a larger beta chain-beta(c), or, in the
      mouse, beta(c) or its close relative beta(IL-3). There is evidence that the
      critical event that initiates signaling is not the approximation of the
      cytoplasmic domains of alpha(IL-3) and beta(IL-3), but is, rather, the formation 
      of a beta-beta homodimer. Many of these studies involved the analyses of receptor
      chimeras where the cytoplasmic domains were derived from alpha(IL-3), beta(c) or 
      beta(IL-3), and the extracellular domains were derived from other cytokine
      receptors, such as the erythropoietin receptor (EpoR). However, evidence that the
      EpoR may also associate with other receptors clouds the interpretation of these
      experiments. Therefore, we reevaluated the structure of the functional IL-3R
      using chimeric receptors with extracellular domains derived not from members of
      the cytokine-receptor family, but from CD8 or CD16. We show, by expression of
      these chimeras in Ba/F3 or CTLL-2 cells, that mitogenic signals were only
      generated by heterodimerization of the cytoplasmic domains of alpha(IL-3) and
      beta(IL-3). Homodimers of either alpha(IL-3) or beta(IL-3), alone or in
      combination, were nonfunctional. Furthermore, the ability of heterodimers to
      stimulate mitogenesis correlated with their ability to induce tyrosine
      phosphorylation of JAK-2. These data suggest that the physiological activation of
      the IL-3R involves the generation of simple heterodimers of alpha(IL-3) and
      beta(IL-3).
FAU - Orban, P C
AU  - Orban PC
AD  - The Biomedical Research Centre, University of British Columbia, Vancouver, BC,
      Canada.
FAU - Levings, M K
AU  - Levings MK
FAU - Schrader, J W
AU  - Schrader JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Interleukin-3)
RN  - 0 (Receptors, Interleukin-3)
RN  - 0 (Recombinant Fusion Proteins)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dimerization
MH  - Humans
MH  - Interleukin-3/*pharmacology
MH  - Mice
MH  - Mitosis/drug effects/*physiology
MH  - Receptors, Interleukin-3/chemistry/*physiology
MH  - Recombinant Fusion Proteins/chemistry/physiology
MH  - Signal Transduction/*drug effects
MH  - Structure-Activity Relationship
MH  - Transfection
EDAT- 1999/09/09 00:00
MHDA- 1999/09/09 00:01
CRDT- 1999/09/09 00:00
PHST- 1999/09/09 00:00 [pubmed]
PHST- 1999/09/09 00:01 [medline]
PHST- 1999/09/09 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Sep 1;94(5):1614-22.