PMID- 10514520
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 42
DP  - 1999 Oct 15
TI  - CIS associates with the interleukin-2 receptor beta chain and inhibits
      interleukin-2-dependent signaling.
PG  - 30266-72
AB  - CIS is a cytokine-induced SH2-containing protein that was originally cloned as an
      interleukin (IL)-3-inducible gene. CIS is known to associate with the IL-3
      receptor beta chain and erythropoietin receptor and to inhibit signaling mediated
      by IL-3 and erythropoietin. We now demonstrate that CIS also interacts with the
      IL-2 receptor beta chain (IL-2Rbeta). This interaction requires the A region of
      IL-2Rbeta (residues 313-382), which also mediates the association of IL-2Rbeta
      with Lck and Jak3. Correspondingly, CIS inhibits functions associated with both
      of these kinases: Lck-mediated phosphorylation of IL-2Rbeta and IL-2-mediated
      activation of Stat5. Thus, we demonstrate that CIS can negatively control at
      least two independent IL-2 signaling pathways. Although a functional SH2 binding 
      domain of CIS was not required for its interaction with IL-2Rbeta in vitro, its
      phosphotyrosine binding capability was essential for the inhibitory action of
      CIS. On this basis, we have generated a mutant form of CIS protein with an
      altered SH2 domain that acts as a dominant negative and should prove useful in
      further understanding CIS action.
FAU - Aman, M J
AU  - Aman MJ
AD  - Laboratory of Molecular Immunology, NHLBI, National Institutes of Health,
      Bethesda, Maryland 20892-1674, USA.
FAU - Migone, T S
AU  - Migone TS
FAU - Sasaki, A
AU  - Sasaki A
FAU - Ascherman, D P
AU  - Ascherman DP
FAU - Zhu, M h
AU  - Zhu Mh
FAU - Soldaini, E
AU  - Soldaini E
FAU - Imada, K
AU  - Imada K
FAU - Miyajima, A
AU  - Miyajima A
FAU - Yoshimura, A
AU  - Yoshimura A
FAU - Leonard, W J
AU  - Leonard WJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Interleukin-2)
RN  - 0 (Milk Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-2)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (cytokine inducible SH2-containing protein)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Line
MH  - DNA-Binding Proteins/metabolism
MH  - Humans
MH  - Immediate-Early Proteins/biosynthesis/genetics/*metabolism
MH  - Interleukin-2/*antagonists & inhibitors/metabolism
MH  - Janus Kinase 1
MH  - *Milk Proteins
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein-Tyrosine Kinases/metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Interleukin-2/*metabolism
MH  - STAT5 Transcription Factor
MH  - *Signal Transduction
MH  - Suppressor of Cytokine Signaling Proteins
MH  - Trans-Activators/metabolism
MH  - Tyrosine/metabolism
MH  - src Homology Domains
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - 10.1074/jbc.274.42.30266 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 15;274(42):30266-72. doi: 10.1074/jbc.274.42.30266.