TKL

The tyrosine kinase-like (TKL) group occupies an intermediate position between serine/threonine and tyrosine kinases, with catalytic domains resembling TKs but autophosphorylation and substrate specificity that often follow serine/threonine rules. Its families include the RAF kinases of the RAS/RAF/MEK/ERK cascade, mixed lineage kinases (MLK), LIM kinases that phosphorylate cofilin to remodel actin, TESK, the interleukin-1 receptor-associated kinases (IRAK1-4) of innate immunity, and the type I and type II receptor serine/threonine kinases for the TGF-beta superfamily. TKL members thus couple immune recognition, TGF-beta signaling and cytoskeletal dynamics to downstream responses. RAF and IRAK4 inhibitors are established or advanced clinical candidates.