Ser/Thr Kinase (丝氨酸/苏氨酸激酶)

Ser/Thr Kinase belongs to the eukaryotic protein kinase (ePK) superfamily and can use ATP to phosphorylate the hydroxyl group of serine or threonine residues in the kinase recognition amino acid sequence. The widely known anticancer targets in the Ser/Thr Kinase family are protein kinase C (PKC) and cyclin-dependent kinases (CDKs). There are two types of Ser/Thr Kinase: one is a kinase that phosphorylates receptor molecules, i.e., receptor protein serine/threonine kinases, such as activated receptor kinases and transforming growth factor β receptor kinases; the other is a kinase that acts as an intracellular signal transduction protein. The latter can phosphorylate several key targets of multiple signaling pathways and affect a variety of biological functions including growth, differentiation, cell cycle progression, and metabolism. This family contains several different groups of kinases, including (1) the CK group of kinases: casein kinases; (2) the AGC group: the kinases protein kinase A (PKA), protein kinase B (PKB or v-akt murine thymoma viral oncogene homolog 1: AKT1), and protein kinase C (PKC); (3) the CAMK group of kinases: Ca²⁺/calmodulin-dependent kinases; (4) the CMGC group of kinases: mos/raf kinases, mitogen-activated kinases (MAPKs), cyclin-dependent kinases (CDKs), and glycogen synthase kinases (GSKs); and (5) the STE group of kinases: homologs of yeast sterile kinases 7, 11, and 20 kinases.Ser/Thr Kinase family regulates the glucocorticoid receptor (GR), a nuclear hormone receptor superfamily protein. For example, MAPK, CDK, PKB/AKT1 and GSK3β can phosphorylate GR at specific residues; PKA, AKT1, PKC, MAPK, AMPK and mTOR can additionally phosphorylate other kinases and/or transcriptional cofactors associated with DNA-associated GR to indirectly regulate GR. It is worth mentioning that p38 MAPK in the MAPK family regulates serine phosphorylation of GR through upstream MAP2K2/4, while another JNK inhibits GR transcriptional activity by enhancing the nuclear export of the receptor^[1][2].

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