Blood 1998,
PMID: 9516124
Ogata, N; Kouro, T; Yamada, A; Koike, M; Hanai, N; Ishikawa, T; Takatsu, K
The human interleukin-5 receptor (hIL-5R) consists of a unique alpha subunit (hIL-5Ralpha) and a common beta subunit (betac) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5). The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated. We analyzed the interaction between hIL-5Ralpha and betac by immunoprecipitation using anti-hIL-5Ralpha and anti-betac monoclonal antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated in the hIL-5-responsive cell line, TF-h5Ralpha. It was observed that IL-5 stimulation induced the recruitment of betac to hIL-5Ralpha, although in the absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and JAK1 were associated with hIL-5Ralpha and betac, respectively. IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, betac, and STAT5. Moreover, IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and betac phosphorylation even in the absence of JAK1 activation. Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2. Detailed study of the C-terminal truncated cytoplasmic domain of hIL-5Ralpha revealed that the cytoplasmic stretch at position 346-387, containing the proline-rich region, is necessary for JAK2 binding. These observations suggest that activation of hIL-5Ralpha-associated JAK2 is indispensable for the IL-5 signaling event.
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Text Mining Data
STAT5 ⊣ IL-5: "
IL-5 stimulation
resulted in tyrosine phosphorylation of JAK2, JAK1, betac, and
STAT5
"
JAK1 ⊣ IL-5: "
IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1 , betac, and STAT5
"
JAK1 → IL-5: "
IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1 , betac, and STAT5
"
JAK1 → JAK2: "
Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2
"
Manually curated Databases
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IRef Biogrid Interaction:
JAK1
—
IL5RA
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
JAK2
—
IL5RA
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
JAK2
—
IL5RA
(direct interaction, pull down)
-
IRef Biogrid Interaction:
CSF2RB
—
IL5RA
(physical association, affinity chromatography technology)
-
IRef Hprd Interaction:
JAK2
—
JAK2
(in vivo)
-
IRef Hprd Interaction:
JAK2
—
JAK2
(in vitro)
-
IRef Hprd Interaction:
JAK1
—
IL5RA
(in vitro)
-
IRef Hprd Interaction:
IL5RA
—
JAK2
(in vitro)
-
IRef Hprd Interaction:
IL5RA
—
JAK2
(in vivo)
-
IRef Hprd Interaction:
CSF2RB
—
IL5RA
(in vivo)
-
IRef Ophid Interaction:
IL5RA
—
JAK2
(aggregation, confirmational text mining)
-
NCI Pathway Database IL5-mediated signaling events:
IL5 (IL5)
→
IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL5-mediated signaling events:
IL5 (IL5)
→
IL5RA/JAK2 complex (IL5RA-JAK2)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL5-mediated signaling events:
IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5)
→
IL5RA/JAK2 complex (IL5RA-JAK2)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL5-mediated signaling events:
IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5)
→
IL5/IL5RA/CSF2RB (hexamer)/JAK2/JAK2 complex (CSF2RB-IL5-IL5RA-JAK2)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL5-mediated signaling events:
IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5)
→
CSF2RB (dimer) complex (CSF2RB)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL5-mediated signaling events:
IL5/IL5RA/CSF2RB (hexamer)/JAK2/JAK2 complex (CSF2RB-IL5-IL5RA-JAK2)
→
CSF2RB (dimer) complex (CSF2RB)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
In total, 11 gene pairs are associated to this article in curated databases