Tpl-2 is a serine/threonine kinase that has been studied extensively in monocytes. Tpl-2 is believed to phosphorylate MEK1/2, which is upstream of ERK1/2, and regulates inflammatory gene expression in response to TLR and IL-1b receptor signaling. In the course of performing proof-of-concept studies using a small molecule inhibitor (SMI) of Tpl-2, we were surprised to see the inhibitor affect cytokine production in human neutrophils. Unlike human monocytes, which respond at least some degree to both Tpl-2 and MEK inhibitors, neutrophils showed a disconnect between Tpl-2 and MEK. A panel of genes in this cell type can be fully blocked by a Tpl-2 SMI, and yet show no response to a MEK SMI, suggesting Tpl-2 mediates its effect through substrates other than MEK. SOURCE: Mark McCreary (mccrearm@gene.com) -  Genentech

Pluto Bioinformatics

GSE84153: Tpl-2 small molecule project