The TKL group
Tyrosine kinase-like kinases are serine-threonine protein kinases named so because of their close sequence similarity to tyrosine kinases. TKLs are well-represented in metazoans and virtually absent from fungi. They are also present in protists such as Apicomplexa parasites, and in photosynthetic organisms. In fact, TKLs are by far the largest group of kinases in land plants, where they often constitute ca. 80% of the plant kinome.
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.
Parkinson Study Group PRECEPT Investigators.
Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease.
Scharpfenecker M, van Dinther M, Liu Z, van Bezooijen RL, Zhao Q, Pukac L, Lö CW, ten Dijke P.
BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis.
J Cell Sci.