The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

Keyhole limpet hemocyanin induces innate immunity via Syk and Erk phosphorylation

“…The lectin receptors and other receptors, such as MR (Tsai et al, 2013[48]), CR3 (Xia et al, 1999[51]), TLRs (Netea et al, 2006[36]) and FcγRs (Vogelpoel et al, 2015[49]), drive Syk signaling cascades (Kerrigan et al, 2010[23]; Hadas et al, 2012[18]; Dennehy et al, 2008[13]; Falker et al, 2014[15]), leading to Syk autophosphorylation and NF-κB activation. The NF-κB activation results in the production of pro-inflammatory cytokines, which in turn induces cellular responses, including apoptosis and phagocytosis (Parsa et al, 2008[38]; Kingeter and Lin, 2012[25]; Falker et al, 2014[15]). In the present study, a Syk inhibitor, Bay 61-3606 hydrochloride, partially suppressed the KLH-induced NF-κB activation, suggesting that Syk would partially associate with the signaling pathways.…”

“…Erk has an important role of fundamental cellular reaction such as differentiation (Falker et al, 2014[15]), inflammatory responses (Roux and Blenis, 2004[44]; Zhang and Liu, 2002[52]) and apoptosis in mammalian cells (Parsa et al, 2008[38]; Roberts and Der, 2007[42]). Several studies reported that Erk was in downstream of these receptors, CR3(Li et al, 2014[27]), MR (Tsai et al, 2013[48]), TLR2 (Richardson et al, 2015[41]; Chen et al, 2015[8]) and FcγRs (Luo et al, 2010[28]; Song et al, 2004[46]).…”

“…These receptors in myeloid cell mainly activate the downstream signaling pathways via spleen tyrosine kinase (Syk) (Osorio and Reis e Sousa, 2011[37]). Syk is one of the common molecules associated with these receptors (Kerrigan and Brown, 2010[23]; Hadas et al, 2012[18]; Dennehy et al, 2008[13]; Falker et al, 2014[15]). The study on F. tularensis phagocytosis also reported that Syk-dependent phagocytosis was controlled through an extracellular signal-regulated kinase (Erk) pathway (Parsa et al, 2008[38]).…”

Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation

“…8 The signaling cascade downstream TLR2/1 in platelets is still unclear in many aspects, but involvement of PI3-K activation has been shown. 8 We have recently shown that platelet stimulation through TLR2/1 with Pam 3 CSK 4 initiates the src/Syk/linker for activation of T cells (LAT)/PLCc2-pathway, 10 known to be activated downstream of FccRII, platelet receptor for immunoglobulin G (IgG). 8 We have recently shown that platelet stimulation through TLR2/1 with Pam 3 CSK 4 initiates the src/Syk/linker for activation of T cells (LAT)/PLCc2-pathway, 10 known to be activated downstream of FccRII, platelet receptor for immunoglobulin G (IgG).…”

Coronary Heart Disease Risk Factors Take a Disproportional Toll on Women

“…2, 3 Interestingly, while the canonical TLR signaling pathway components are expressed in platelets, 4 TLRs have also been shown to signal through non-canonical pathways including integrin and ITAM activation pathways to name a few. 5 Thus it is not surprising that certain TLRs in platelets have been shown to have a pro-inflammatory and a pro-thrombotic effect. Ligation of TLRs for example may have the potential to signal in a pro-thrombotic manner by either directly causing (TLR9 and TLR2/1 heterodimer) 6, 7 or potentiating aggregation (TLR4).…”