Human kinases and signaling proteins

Human kinases and signaling proteins encompass a broad array of molecules that regulate nearly every aspect of cellular life by transmitting signals from the cell surface to the nucleus (Manning et al., 2002, Science). Kinases, which make up the human kinome of approximately 518 enzymes, catalyze the transfer of phosphate groups to specific substrates, thereby altering their activity, localization, or stability (UniProt Consortium, 2024). Signaling proteins include not only these enzymes but also receptors, adaptors, and transcription factors that form intricate pathways like the MAPK/ERK or PI3K/AKT cascades (NCBI, 2023, Signal Transduction). Dysregulation of these proteins, often through mutations or overexpression, is a primary driver of oncogenesis, chronic inflammation, and metabolic disorders (Roskoski, 2023, Pharmacological Research). Consequently, they are major therapeutic targets, with hundreds of small-molecule inhibitors and monoclonal antibodies developed to modulate their activity (Bhullar et al., 2018, Molecular Cancer). However, the complexity and crosstalk within these signaling networks often lead to challenges such as drug resistance and off-target toxicities due to the structural similarity between different kinase domains (Zhang et al., 2009, Nature Reviews Cancer).

Other names

Human kinomeProtein kinasesSignal transduction proteinsSignaling molecules

Drugs targeting these proteins typically act as competitive inhibitors at the ATP-binding site of kinases, allosteric modulators, or monoclonal antibodies that block ligand-receptor interactions to prevent downstream signal propagation.