TITLE:
Role of Protein Kinase Cδ-Mediated Spleen Tyrosine Kinase (Syk) Phosphorylation on Ser in the Amplification of Oral Mucosal Inflammatory Responses to Porphyromonas gingivalis
AUTHORS:
Bronislaw L. Slomiany, Amalia Slomiany
KEYWORDS:
P. gingivalis, Oral Mucosa, PKCδ, Syk Activation, Ser/Tyr Phosphorylation
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.6 No.3,
March
14,
2018
ABSTRACT: The signaling events
underlying oral mucosal inflammatory responses to P. gingivalis and its key endotoxin, lipopolysaccharide (LPS),
relay primarily on the LPS engagement of Toll-like receptor-4 (TLR4), and the
activation of IκB-kinase complex (IKK) and
mitogen-activated protein kinases (MAPKs that exert their control over
transcription factors implicated in the regulation of iNOS and COX-2
proinflammatory genes expression). Since
spleen tyrosine kinase (Syk) has emerged recently as a major amplifier in the
production of proinflammatory mediators, we investigated the process of
recruitment and interaction of Syk with TLR4 in salivary gland acinar cells in
response to P. gingivalis LPS. Our
findings revealed that stimulation of the acinar cells with the LPS leads to protein kinase Cδ (PKCδ)-mediated phosphorylation of Syk on Ser which results in its
localization with the membrane associated TLR4 complex and the activation
through phosphorylation on Tyr. Further, our results support the involvement of
Syk in the amplification of transcription factors involved in the assembly and
expression of transcription complexes associated with the induction in COX-2
and iNOS genes. Therefore, our data suggest that PKCδ is a primary linchpin affecting the Syk recruitment to the
membrane localized TLR4, and hence affects the efficiency of the kinase
activation and the magnitude of oral mucosal inflammatory response to P. gingivalis.