PMID- 10409622
OWN - NLM
STAT- MEDLINE
DCOM- 19990826
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 30
DP  - 1999 Jul 23
TI  - Characterization of the cytoplasmic domain of interleukin-13 receptor-alpha.
PG  - 20818-25
AB  - Interleukin (IL)-13 and IL-4 are pleiotropic immunoregulatory cytokines that
      share many overlapping biological properties reflecting the fact that both can
      utilize a receptor complex composed of the IL-4 receptor-alpha (IL-4Ralpha) chain
      and the IL-13Ralpha chain. The cytoplasmic domain of the IL-13Ralpha is 60 amino 
      acids long and is essential for IL-13-dependent growth. It contains a Pro-rich
      domain in the membrane-proximal region and two Tyr residues. Here we show that a 
      truncated IL-13Ralpha, lacking the 38 carboxyl-terminal residues but retaining
      the Pro-rich region, can support IL-13-dependent proliferation, although with
      reduced efficiency. A Y402F mutant of the cytoplasmic domain of IL-13Ralpha
      supported normal IL-13-induced growth. However, tyrosine phosphorylation of
      signal transducer and activator of transcription 3 (STAT3), which we show is
      induced by IL-13 and IL-4 in cells that express the IL-13Ralpha, was
      significantly reduced. The cytoplasmic domain of IL-13Ralpha was constitutively
      associated with STAT3, Tyk2, and Janus kinase 1 (JAK1). IL-13-induced tyrosine
      phosphorylation of IL-13Ralpha in vivo could not be detected using anti-Tyr(P)
      antibodies. A glutathione S-transferase fusion protein of the cytoplasmic domain 
      of IL-13Ralpha was phosphorylated on tyrosine in vitro by JAK1, JAK3, and Tyk2,
      although the tyrosine phosphorylation events mediated by Tyk2 and JAK3 were not
      detectable using anti-phosphotyrosine antibodies. These data, together with the
      demonstration that IL-13Ralpha associates constitutively with Tyk2 and that
      Tyr-402 is involved in IL-13-induced phosphorylation of STAT3, suggest that the
      latter is mediated by Tyk2. Tyrosine phosphorylation of STAT3, which was not
      necessary for IL-13-induced proliferation, may account for some of the effects of
      IL-4 and IL-13 on the function of their targets.
FAU - Orchansky, P L
AU  - Orchansky PL
AD  - The Biomedical Research Centre, The University of British Columbia, Vancouver V6T
      1Z3, British Columbia, Canada.
FAU - Kwan, R
AU  - Kwan R
FAU - Lee, F
AU  - Lee F
FAU - Schrader, J W
AU  - Schrader JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (IL13RA1 protein, human)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-13 Receptor alpha1 Subunit)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-13)
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - Cytoplasm/metabolism
MH  - Humans
MH  - Interleukin-13/*metabolism
MH  - Interleukin-13 Receptor alpha1 Subunit
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Precipitin Tests
MH  - *Receptors, Interleukin/chemistry/genetics/metabolism
MH  - Receptors, Interleukin-13
MH  - Signal Transduction
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - 10.1074/jbc.274.30.20818 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 23;274(30):20818-25. doi: 10.1074/jbc.274.30.20818.