Loading...
Phosphorylation on Syk Y342 is important for both ITAM and hemITAM signaling in platelets
Kostyak, John C. Mauri, Benjamin Dangelmaier, Carol Vari, Hymavathi Reddy Patel, Akruti Wright, Monica Reddy, Haritha Tsygankov, Alexander Y. Kunapuli, Satya P.
Kostyak, John C.
Mauri, Benjamin
Dangelmaier, Carol
Vari, Hymavathi Reddy
Patel, Akruti
Wright, Monica
Reddy, Haritha
Tsygankov, Alexander Y.
Kunapuli, Satya P.
Citations
Altmetric:
Genre
Journal article
Date
2022-06-24
Advisor
Committee member
Department
Cardiovascular Sciences
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
http://dx.doi.org/10.1016/j.jbc.2022.102189
Abstract
Immune cells express receptors bearing an immune tyrosine activation motif (ITAM) containing two YXXL motifs or hemITAMs containing only one YXXL motif. Phosphorylation of the ITAM/hemITAM is mediated by Src family kinases allowing for the binding and activation of spleen tyrosine kinase (Syk). It is believed that Syk must be phosphorylated on tyrosine residues for activation, and Tyr342, а conserved tyrosine in the interdomain B region, has been shown to be critical for regulating Syk in FcεR1-activated mast cells. Syk is a key mediator of signaling pathways downstream of several platelet pathways including the ITAM bearing glycoprotein VI (GPVI)/Fc receptor gamma chain collagen receptor and the hemITAM containing C-type lectin-like receptor-2 (CLEC-2). Since platelet activation is a crucial step in both hemostasis and thrombosis, we evaluated the importance of Syk Y342 in these processes by producing an Syk Y342F knock-in mouse. When using a CLEC-2 antibody as an agonist, reduced aggregation and secretion were observed in Syk Y342F mouse platelets when compared with control mouse platelets. Platelet reactivity was also reduced in response to the GPVI agonist collagen-related peptide. Signaling initiated by either GPVI or CLEC-2 was also greatly inhibited, including Syk Y519/520 phosphorylation. Hemostasis, as measured by tail bleeding time, was not altered in Syk Y342F mice, but thrombus formation in response to FeCl3 injury was prolonged in Syk Y342F mice. These data demonstrate that phosphorylation of Y342 on Syk following stimulation of either GPVI or CLEC-2 receptors is important for the ability of Syk to transduce a signal.
Description
Citation
John C. Kostyak, Benjamin Mauri, Carol Dangelmaier, Hymavathi Reddy Vari, Akruti Patel, Monica Wright, Haritha Reddy, Alexander Y. Tsygankov, Satya P. Kunapuli, Phosphorylation on Syk Y342 is important for both ITAM and hemITAM signaling in platelets, Journal of Biological Chemistry, Volume 298, Issue 8, 2022, 102189, ISSN 0021-9258, https://doi.org/10.1016/j.jbc.2022.102189.
Citation to related work
Elsevier
Has part
Journal of Biological Chemistry (JBC), Vol. 298, Iss. 8
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu