Family Description Reference
                                                                                      Conventional Family
AGC Named after Protein Kinase A, G and C families, consisting of 60 members across 16 families of cytoplasmic serine/threonine kinases, regulated by secondary messengers. E.g.: PKC and PKA. Mutation and dysregulation linked to many conditions such as diabetes and cancer. [41,42]
CaMK Named after Calmodulin/Calcium regulated kinases, the CaMK group consists of both calcium and non-calcium regulated kinases. E.g.: CaMK I, CaMK II and CaMK IV. CaMK II is essential for NF-κB activation following TCR ligation. [43,44]
CK1 Named after Casein kinase 1 (CK1), these monomeric serine/threonine selective kinases are evolutionary conserved within eukaryotes. CK1 kinases regulate diverse functions form circadian rhythm, Wnt signalling, DNA replication and RNA metabolism. [45]
CMGC The CMGC group includes the evolutionarily conserved, cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs) and CDK-like kinases (CLKs). Their roles include, cell cycle regulation, immune signalling mediated downstream gene expression, regulating cell proliferation and apoptosis. [32,46-49]
RGC The receptor guanylate cyclases (RGCs) synthesize cyclic GMP from GTP. RGCs are membrane bound and are activated by calcium or the binding of atrial naturetic peptide or related peptides. E.g.: GC-A and GC-G. [50,51]
STE Serine threonine kinases (STE) are subdivided into 3 main families Ste7, Ste11 and Ste20, which sequentially activate each other and MAPK members. Ste20 kinases (MAP4K) act on Ste11 kinases (MAP3K), which activate Ste7 kinases (MAP2K, MEK, MKKs). These families have distinct roles in T lymphocyte activation. [32,52]
TK Tyrosine kinases (TK) evolutionarily conserved in mammals, phosphorylate tyrosine residues. The TK are divided into receptor and non-receptor (cytoplasmic) tyrosine kinases (CTK). The receptor tyrosine kinases are activated by extracellular signals such as growth factors at the cell surface. The CTK include, Src kinases such as Tec and janus kinases (JAK). [53,54]
TKL The tyrosine kinases-like (TKL) group has close sequence similarity to the TKs. These diverse, serine/threonine kinases, are subdivided into 7 major families, including the RAF, IRAK and RIPK families. The TKL kinases are involved in a wide range of immune cell processes including cell growth, Toll like receptor (TLR) and IL-1 signalling and cell death. [55-57]
                                                                                    Atypical Family
Alpha α-Kinases have low sequence homology with other conventional kinases and have known functions in protein translation, intracellular transport, cell migration and proliferation. E.g.: elongation factor 2 kinase and Dictyostelium myosin heavy chain kinases [58]
PIKK The phosphoinositide 3-kinase-related kinases (PIKK) are involved in DNA damage, nutrient dependent signalling mRNA decay. E.g.: the mammalian target of rapamycin (mTOR), has been well studied in the context of T cell metabolism and differentiation. [33,59]
PDK The mitochondrial pyruvate dehydrogenase kinases (PDKs), required for oxidative metabolism mediate the phosphorylation of pyruvate dehydrogenase. There are four known mammalian isoforms; PDHK1-4, and these regulate the balance between glycolysis and lipid metabolism. [60,61]
RIO The right open reading frame (RIO) kinases are expressed in archea to humans. Their functions include, ribosome biogenesis and chromosome maintenance, although the precise substrate of the RIO kinases is unknown. RIO kinases from the ruminant nematode, Haemonchus contortus have been targeted for nematocidal drugs. [62,63]
Table 1: Kinase families and their functions.