Feedback Regulation of Syk by Protein Kinase C in Human Platelets.
Adenosine Diphosphate
/ pharmacology
Blood Platelets
/ cytology
Calcium
/ metabolism
Crotalid Venoms
/ pharmacology
Feedback, Physiological
/ drug effects
Humans
Indoles
/ pharmacology
Lectins, C-Type
Maleimides
/ pharmacology
Phospholipase C gamma
/ metabolism
Phosphorylation
/ drug effects
Platelet Aggregation
/ drug effects
Protein Kinase C
/ antagonists & inhibitors
Syk Kinase
/ antagonists & inhibitors
Viper Venoms
/ pharmacology
cyclic adenosine monophosphate (cAMP)
glycoprotein Ibα
glycoprotein VI
platelets
protein kinase C
spleen tyrosine kinase (Syk)
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
25 Dec 2019
25 Dec 2019
Historique:
received:
28
11
2019
revised:
20
12
2019
accepted:
20
12
2019
entrez:
29
12
2019
pubmed:
29
12
2019
medline:
7
5
2020
Statut:
epublish
Résumé
The spleen tyrosine kinase (Syk) is essential for immunoreceptor tyrosine-based activation motif (ITAM)-dependent platelet activation, and it is stimulated by Src-family kinase (SFK)-/Syk-mediated phosphorylation of Y352 (interdomain-B) and Y525/526 (kinase domain). Additional sites for Syk phosphorylation and protein interactions are known but remain elusive. Since Syk S297 phosphorylation (interdomain-B) was detected in platelets, we hypothesized that this phosphorylation site regulates Syk activity via protein kinase C (PKC)-and cyclic adenosine monophosphate (cAMP)-dependent pathways. ADP, the GPVI-agonist convulxin, and the GPIbα-agonist echicetin beads (EB) were used to stimulate human platelets with/without effectors. Platelet aggregation and intracellular messengers were analyzed, along with phosphoproteins, by immunoblotting using phosphosite-specific antibodies or phos-tags. ADP, convulxin, and EB upregulated Syk S297 phosphorylation, which was inhibited by iloprost (cAMP pathway). Convulxin-stimulated Syk S297 phosphorylation was stoichiometric, transient, abolished by the PKC inhibitor GF109203X, and mimicked by the PKC activator PDBu. Convulxin/EB stimulated Syk S297, Y352, and Y525/526 phosphorylation, which was inhibited by SFK and Syk inhibitors. GFX and iloprost inhibited convulxin/EB-induced Syk S297 phosphorylation but enhanced Syk tyrosine (Y352/Y525/526) and substrate (linker adaptor for T cells (LAT), phospholipase γ2 (PLC γ2)) phosphorylation. GFX enhanced convulxin/EB-increases of inositol monophosphate/Ca
Identifiants
pubmed: 31881809
pii: ijms21010176
doi: 10.3390/ijms21010176
pmc: PMC6981976
pii:
doi:
Substances chimiques
Crotalid Venoms
0
Indoles
0
Lectins, C-Type
0
Maleimides
0
Viper Venoms
0
echicetin
148937-32-0
convulxin
37206-04-5
Adenosine Diphosphate
61D2G4IYVH
SYK protein, human
EC 2.7.10.2
Syk Kinase
EC 2.7.10.2
Protein Kinase C
EC 2.7.11.13
Phospholipase C gamma
EC 3.1.4.3
bisindolylmaleimide I
L79H6N0V6C
Calcium
SY7Q814VUP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bundesministerium für Bildung und Forschung
ID : 01EO1003
Organisme : Bundesministerium für Bildung und Forschung
ID : 01EO1503
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