PMID- 10377387
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 13
DP  - 1999 Jun 22
TI  - Identification of SH2-bbeta as a potent cytoplasmic activator of the tyrosine
      kinase Janus kinase 2.
PG  - 7172-7
AB  - Janus kinases (JAKs) are cytoplasmic tyrosine kinases critical for signaling by
      growth hormone (GH) and many other ligands that bind to members of the cytokine
      receptor superfamily. SH2-Bbeta was previously identified as a JAK2-interacting
      protein that is tyrosyl phosphorylated in response to GH and other cytokines that
      activate JAK2. In this study, we examined whether SH2-Bbeta alters the activity
      of JAK2. SH2-Bbeta, when coexpressed with JAK2, significantly increased the
      tyrosyl phosphorylation of JAK2 and multiple other cellular proteins and
      stimulated the kinase activity of JAK2 by approximately 20-fold. Coexpression of 
      SH2-Bbeta with JAK2 dramatically increased tyrosyl phosphorylation of signal
      transducer and activator of transcription (Stat)5B and Stat3, physiological
      substrates of JAK2. SH2-Bbeta(R555E) with a defective Src homology 2 domain was
      unable to stimulate JAK2 and JAK2-mediated tyrosyl phosphorylation of Stat5B and 
      Stat3. More importantly, SH2-Bbeta enhanced GH-induced tyrosyl phosphorylation of
      endogenous JAK2 and ligand-induced tyrosyl phosphorylation of Stat5B by
      endogenous JAK2. In contrast, SH2-Bbeta did not potentiate the activation of
      other tyrosine kinases including the receptors for platelet-derived growth
      factor, epidermal growth factor, or nerve growth factor (TrkA), tyrosine kinases 
      that also bind SH2-Bbeta. These data demonstrate that SH2-Bbeta is a potent
      cytoplasmic activator of JAK2 and is thereby expected to be an important cellular
      regulator of signaling by GH and other hormones and cytokines that activate JAK2.
FAU - Rui, L
AU  - Rui L
AD  - Department of Physiology, University of Michigan Medical School, Ann Arbor, MI
      48109-0622, USA.
FAU - Carter-Su, C
AU  - Carter-Su C
LA  - eng
GR  - P30-AR20557/AR/NIAMS NIH HHS/United States
GR  - P30 CA 46592/CA/NCI NIH HHS/United States
GR  - P30 CA046592/CA/NCI NIH HHS/United States
GR  - R37 DK034171/DK/NIDDK NIH HHS/United States
GR  - P60 DK020572/DK/NIDDK NIH HHS/United States
GR  - R01 DK034171/DK/NIDDK NIH HHS/United States
GR  - P60-DK 20572/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Sh2bpsm1 protein, mouse)
RN  - 0 (Stat5b protein, mouse)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - COS Cells
MH  - Carrier Proteins/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Enzyme Activation
MH  - Janus Kinase 2
MH  - Mice
MH  - *Milk Proteins
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - STAT5 Transcription Factor
MH  - Trans-Activators/metabolism
MH  - src Homology Domains
PMC - PMC22043
EDAT- 1999/06/23 00:00
MHDA- 1999/06/23 00:01
CRDT- 1999/06/23 00:00
PHST- 1999/06/23 00:00 [pubmed]
PHST- 1999/06/23 00:01 [medline]
PHST- 1999/06/23 00:00 [entrez]
AID - 10.1073/pnas.96.13.7172 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7172-7. doi:
      10.1073/pnas.96.13.7172.