PMID- 10064597
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 5
DP  - 1999 Mar 1
TI  - The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through
      binding in the activation loop.
PG  - 1309-20
AB  - The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes
      involved in cell growth, differentiation and transformation through their
      association with cytokine receptors. However, compared with other kinases, little
      is known about cellular regulators of the JAKs. We have recently identified a
      JAK-binding protein (JAB) that inhibits JAK signaling in cells. In the studies
      presented here we demonstrate that JAB specifically binds to the tyrosine residue
      (Y1007) in the activation loop of JAK2, whose phosphorylation is required for
      activation of kinase activity. Binding to the phosphorylated activation loop
      requires the JAB SH2 domain and an additional N-terminal 12 amino acids (extended
      SH2 subdomain) containing two residues (Ile68 and Leu75) that are conserved in
      JAB-related proteins. An additional N-terminal 12-amino-acid region (kinase
      inhibitory region) of JAB also contributes to high-affinity binding to the JAK2
      tyrosine kinase domain and is required for inhibition of JAK2 signaling and
      kinase activity. Our studies define a novel type of regulation of tyrosine
      kinases and might provide a basis for the design of specific tyrosine kinase
      inhibitors.
FAU - Yasukawa, H
AU  - Yasukawa H
AD  - Institute of Life Science, Kurume University, Aikawa-machi 2432-3 Kurume
      839-0861, Japan.
FAU - Misawa, H
AU  - Misawa H
FAU - Sakamoto, H
AU  - Sakamoto H
FAU - Masuhara, M
AU  - Masuhara M
FAU - Sasaki, A
AU  - Sasaki A
FAU - Wakioka, T
AU  - Wakioka T
FAU - Ohtsuka, S
AU  - Ohtsuka S
FAU - Imaizumi, T
AU  - Imaizumi T
FAU - Matsuda, T
AU  - Matsuda T
FAU - Ihle, J N
AU  - Ihle JN
FAU - Yoshimura, A
AU  - Yoshimura A
LA  - eng
GR  - P0 HL53749/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphopeptides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SOCS1 protein, human)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
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)
SB  - IM
MH  - Amino Acid Sequence
MH  - Carrier Proteins/*genetics/metabolism
MH  - Cell Line
MH  - Enzyme Activation/genetics
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Janus Kinase 2
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphopeptides/chemistry
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors
MH  - *Proto-Oncogene Proteins
MH  - *Repressor Proteins
MH  - Sequence Deletion
MH  - Signal Transduction
MH  - Suppression, Genetic
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling Proteins
MH  - src Homology Domains
PMC - PMC1171221
EDAT- 1999/03/04 00:00
MHDA- 1999/03/04 00:01
CRDT- 1999/03/04 00:00
PHST- 1999/03/04 00:00 [pubmed]
PHST- 1999/03/04 00:01 [medline]
PHST- 1999/03/04 00:00 [entrez]
AID - 10.1093/emboj/18.5.1309 [doi]
PST - ppublish
SO  - EMBO J. 1999 Mar 1;18(5):1309-20. doi: 10.1093/emboj/18.5.1309.