Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation

Details

Serval ID
serval:BIB_2BF65B5FCBFD
Type
Article: article from journal or magazin.
Collection
Publications
Title
Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation
Journal
Mol Cell Biol
Author(s)
Zhou Y. J., Magnuson K. S., Cheng T. P., Gadina M., Frucht D. M., Galon J., Candotti F., Geahlen R. L., Changelian P. S., O'Shea J. J.
ISSN
0270-7306 (Print)
ISSN-L
0270-7306
Publication state
Published
Issued date
06/2000
Peer-reviewed
Oui
Volume
20
Number
12
Pages
4371-80
Language
english
Notes
Zhou, Y J
Magnuson, K S
Cheng, T P
Gadina, M
Frucht, D M
Galon, J
Candotti, F
Geahlen, R L
Changelian, P S
O'Shea, J J
eng
Mol Cell Biol. 2000 Jun;20(12):4371-80.
Abstract
Interleukin-2 (IL-2) activates several different families of tyrosine kinases, but precisely how these kinases interact is not completely understood. We therefore investigated the functional relationships among Jak3, Lck, and Syk in IL-2 signaling. We first observed that in the absence of Jak3, both Lck and Syk had the capacity to phosphorylate Stat3 and Stat5a. However, neither supported IL-2-induced STAT activation, nor did dominant negative alleles of these kinases inhibit. Moreover, pharmacological abrogation of Lck activity did not inhibit IL-2-mediated phosphorylation of Jak3 and Stat5a. Importantly, ligand-dependent Syk activation was dependent on the presence of catalytically active Jak3, whereas Lck activation was not. Interestingly, Syk functioned as a direct substrate of Jak1 but not Jak3. Additionally, Jak3 phosphorylated Jak1, whereas the reverse was not the case. Taken together, our data support a model in which Lck functions in parallel with Jak3, while Syk functions as a downstream element of Jaks in IL-2 signaling. Jak3 may regulate Syk catalytic activity indirectly via Jak1. However, IL-2-mediated Jak3/Stat activation is not dependent on Lck or Syk. While the essential roles of Jak1 and Jak3 in signaling by gammac-utilizing cytokines are clear, it will be important to dissect the exact contributions of Lck and Syk in mediating the effects of IL-2 and related cytokines.
Keywords
Animals, Cell Line, DNA-Binding Proteins/*physiology, Enzyme Activation, Enzyme Precursors/physiology, Humans, Interleukin-2/*physiology, Intracellular Signaling Peptides and Proteins, Janus Kinase 3, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/physiology, *Milk Proteins, Phosphorylation, Protein-Tyrosine Kinases/*physiology, Receptors, Interleukin-2/physiology, STAT5 Transcription Factor, *Signal Transduction, Syk Kinase, Trans-Activators/*physiology, Tumor Suppressor Proteins
Pubmed
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01/11/2017 11:29
Last modification date
03/03/2018 15:26
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