PMID- 8580378
OWN - NLM
STAT- MEDLINE
DCOM- 19960319
LR  - 20191101
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 7
IP  - 7
DP  - 1995 Oct
TI  - Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and 
      STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain.
PG  - 689-700
AB  - A number of cytokines and growth factors use the JAK-STAT pathway to signal from 
      the cell membrane to the nucleus. While homodimerizing cytokine receptors may 
      transmit signal via a single form of JAK (i.e. growth hormone receptors), several 
      multicomponent cytokine receptors have been shown to require simultaneous 
      activation of pairs of different JAK kinases (i.e. interferon receptors). Recent 
      evidence for a preferential coupling of JAK3 to interleukin-2 receptor-gamma 
      (IL-2R gamma) and JAK1 to IL-2R beta supports the concept of 
      heterotrans-activation of JAK1 and JAK3 caused by IL-2-induced heterodimerization 
      of their receptor partners. The present study verified the ability of IL-2 to 
      cause tyrosine phosphorylation and activation of JAK1 and JAK3, but demonstrated 
      that IL-2 stimulated JAK3 to a significantly larger extent than JAK1 in human T 
      lymphocytes and the YT cell line. This conclusion was based upon several 
      independent criteria, including more vigorous tyrosine phosphorylation of JAK3, 
      more marked enzymatic activation of JAK3 as well as higher abundance of JAK3 in 
      activated IL-2 receptor complexes. Furthermore, when human IL-2R beta was stably 
      expressed in murine BA/F3 cells, robust IL-2-induced proliferation and JAK3 
      activation occurred without detectable involvement of either JAK1, JAK2 or TYK2. 
      We therefore propose that IL-2 receptor signal transduction does not depend on 
      equimolar heterodimerization of JAK1 and JAK3 following IL-2-induced 
      heterodimerization of IL-2R beta and IL-2R gamma. Nonetheless, a 
      membrane-proximal region of human IL-2R beta (Asn240-Leu335) was critical for 
      JAK3 activation, and the amount of JAK3 present in activated IL-2 receptor 
      complexes increased with time, suggesting that stabilization of JAK3 binding to 
      the receptor complex relies on both IL-2R beta and IL-2R gamma. Moreover, STAT5 
      was found to be the predominant STAT transcription factor used by IL-2 in human T 
      cells, and specifically required a COOH-terminal region of IL-2R beta 
      (Ser386-Val525), while STAT5 recruitment was not correlated to activation of 
      IL-2R gamma or JAK3.
FAU - Kirken, R A
AU  - Kirken RA
AD  - Department of Cytokine Molecular Mechanisms Section, National Cancer Institute, 
      Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
FAU - Rui, H
AU  - Rui H
FAU - Malabarba, M G
AU  - Malabarba MG
FAU - Howard, O M
AU  - Howard OM
FAU - Kawamura, M
AU  - Kawamura M
FAU - O'Shea, J J
AU  - O'Shea JJ
FAU - Farrar, W L
AU  - Farrar WL
LA  - eng
GR  - 5FO5 TWO4300-02/TW/FIC 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  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Mitogens)
RN  - 0 (Receptors, Interleukin-2)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (JAK3 protein, human)
RN  - EC 2.7.10.2 (Jak1 protein, mouse)
RN  - EC 2.7.10.2 (Jak3 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.10.2 (Janus Kinase 3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Catalysis
MH  - Cell Line
MH  - Enzyme Activation
MH  - Evaluation Studies as Topic
MH  - Humans
MH  - Janus Kinase 1
MH  - Janus Kinase 3
MH  - Lymphocyte Activation/*physiology
MH  - Mice
MH  - Mitogens/physiology
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Interleukin-2/*metabolism
MH  - Signal Transduction/*physiology
MH  - T-Lymphocytes/*metabolism
MH  - Transcription Factors/biosynthesis
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - S1043466685700816 [pii]
AID - 10.1006/cyto.1995.0081 [doi]
PST - ppublish
SO  - Cytokine. 1995 Oct;7(7):689-700. doi: 10.1006/cyto.1995.0081.