PMID- 10374881
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20190915
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 13
IP  - 5
DP  - 1999 May
TI  - APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2
      (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl.
PG  - 760-7
AB  - We cloned a novel adaptor protein, APS (adaptor molecule containing Pleckstrin
      homology (PH) and Src Homology-2 (SH2) domains), which was tyrosine
      phosphorylated in response to c-kit or B cell receptor stimulation. Here, we
      report that APS was tyrosine phosphorylated by Janus kinase-2 (JAK2) at its
      C-terminal tyrosine residue and interacted with c-Cbl. Forced expression of APS
      in an erythropoietin (EPO)-dependent hematopoietic cell line resulted in reduced 
      activation of STAT5 but not cell proliferation in response to EPO. APS bound to
      the phosphorylated tyrosine residue, Y343 of the erythropoietin receptor
      cytoplasmic domain. Co-expression of APS and c-Cbl, but not expression of either 
      alone inhibited EPO-dependent STAT5 activation in 293 cells. This required the
      C-terminal phosphorylation site, as well as PH and SH2 domains of APS. Therefore,
      one of the major functions of APS is in recruitment of c-Cbl into the
      receptor/JAK complex, thereby inhibiting JAK signaling activity.
FAU - Wakioka, T
AU  - Wakioka T
AD  - Institute of Life Science, Department of Orthopaedic Surgery, Kurume University, 
      Japan.
FAU - Sasaki, A
AU  - Sasaki A
FAU - Mitsui, K
AU  - Mitsui K
FAU - Yokouchi, M
AU  - Yokouchi M
FAU - Inoue, A
AU  - Inoue A
FAU - Komiya, S
AU  - Komiya S
FAU - Yoshimura, A
AU  - Yoshimura A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Cytokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Erythropoietin)
RN  - 0 (SH2B2 protein, human)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 11096-26-7 (Erythropoietin)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 6.3.2.- (CBL protein, human)
SB  - IM
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Cell Line
MH  - Cytokines/pharmacology
MH  - DNA-Binding Proteins/*physiology
MH  - Erythropoietin/physiology
MH  - Humans
MH  - Janus Kinase 2
MH  - *Milk Proteins
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*physiology
MH  - Proteins/*physiology
MH  - Proto-Oncogene Proteins/*physiology
MH  - Proto-Oncogene Proteins c-cbl
MH  - Receptors, Erythropoietin/metabolism
MH  - STAT5 Transcription Factor
MH  - *Signal Transduction
MH  - Trans-Activators/*physiology
MH  - Tyrosine/metabolism
MH  - *Ubiquitin-Protein Ligases
MH  - *src Homology Domains
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1038/sj.leu.2401397 [doi]
PST - ppublish
SO  - Leukemia. 1999 May;13(5):760-7. doi: 10.1038/sj.leu.2401397.