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Protein kinases are typically classified primarily according to sequence similarity, which in turn generally reflects the sequence of their substrates and their biological functions. In some cases however, biological functions cut across this kind of classification.

===MAPK signaling===

One of the canonical signaling pathways involves a relay of kinases phosphorylating other kinases. The ultimate kinase is MAP Kinase, which phosphorylates transcription factors and leads to changes in gene expression. Upstream of that is a MAP Kinase Kinase (MAP2K), and upstream of that, sequentially are MAP3K and MAP4K genes. The MAPK genes are all found within the CMGC group, closely realted to the cyclin-dependent kinases. However, MAP2K and MAP3K genes come from the STE group, while MAP4K genes come from both the STE group (STE20 family) and the TKL group (in the Raf and MLK families). Conversely, many members of the STE20 family do not appear to function as traditional MAP4K genes.