Tyrosine kinase-like (TKL) kinases are a diverse group of serine-threonine protein kinases with sequence similarity to tyrosine kinases (TK) but lacking TK-specific motifs. The TKL group is the most recently-defined and most diverse of the standard kinase groups. Families within the group are relatively weakly related to each other. Over half of plant kinomes is made of TKL kinases, and they include receptor kinases and possible tyrosine-specific kinases in other lineages.
Prominent mebers are the the Raf family kinases, acting as important components of the MAP kinase pathway, and TGF beta receptors involved in in many cellular processes such as cell growth, cell differentiation and apoptosis. In animals, TKLs are tightly integrated with other important signalling pathways and thus also play fundamental roles. For example, Mixed Lineage Kinases (MLKs) are known to be responsible for activating apoptotic pathways implicated in the pathogenesis of Parkinson disease. The inhibitor CEP-1347 inhibits MLKs to enhance neuronal survival in a number of clinical models and has entered clinical trials. The TGFβ type-I receptor activin receptor-like kinase 1 (ALK1, a TKL kinase) and its co-receptor endoglin play fundamental roles in angiogenesis and vascular development. ALK1 is a signalling receptor for bone morphogenetic protein-9 (BMP-9) in endothelial cells.