Hi Anjali Roy,
You might find general answer to your question in the paper of Kubo-Murai et al “Protein kinase C delta binds TIRAP/Mal to participate in TLR signaling”, published in Mol Immunol. 2007, 44(9):2257-64. They demonstrated that signaling through toll-like receptor family members results in a proximal event that involves direct binding of adaptor proteins to the receptors. Thus TIRAP/Mal, an adaptor protein for TLR2 and TLR4, binds protein kinase Cdelta (PKCdelta). TIRAP/Mal GST-fusion protein and a TIRAP/Mal antibody were able to precipitate PKCdelta from rat peritoneal macrophage and THP1 cell lysates. Truncation mutants of TIRAP/Mal showed that the TIR domain of TIRAP/Mal is responsible for binding. TLR2- and TLR4-mediated phosphorylation of p38 MAPK, IKK, and IkappaB in RAW264.7 cells were abolished by depletion of PKCdelta. Results obtained by Kubo-Murai et al suggest that PKCdelta binding to TIRAP/Mal promotes TLR signaling events.
More mechanistic answer to your very point may be found in the paper of Mondrinos, Kilpartrick et al. entitled “Protein kinase C and acute respiratory distress syndrome”, published in Shock. 2013, 39(6):467-79. The authors summarized recent research efforts in anti-inflammatory drug development have focused on identifying common control points in multiple signaling pathways. The protein kinase kinases specific PKC isoforms (as well as deletion of PKCs in mice) exerts protective effects in various experimental models of lung injury. Furthermore, PKC isoforms have been implicated in inflammatory processes that may be involved in the pathophysiologic changes that result in ARDS, including activation of innate immune and endothelial cells, neutrophil trafficking to the lung, regulation of alveolar epithelial barrier functions, and control of neutrophil proinflammatory and prosurvival signaling. This review focuses on the mechanistic involvement of PKC isoforms in the pathogenesis exemplified here by ARDS.
Best wishes,
Ilya Tsyrlov
Hello Ilya Tsyrlov,
Thank you for taking out time and responding. I had already refereed these papers. I am more interested in finding the particular interacting residues.
In Kubo-Murai et al paper they had mentioned that TIR domain interact with PKC delta. But they had not told which residues of PKC delta are involved in this interaction.
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