Mitogen-activated protein kinase (MAPK) family (MAPK)

Mitogen-activated protein kinases (MAPKs) are a family of evolutionarily conserved serine/threonine-specific protein kinases that regulate fundamental cellular processes including proliferation, differentiation, motility, and survival (Source: Pearson et al., 2001, Endocrine Reviews). The family is primarily composed of three well-characterized subfamilies: the extracellular signal-regulated kinases (ERK1/2), the c-Jun N-terminal kinases (JNK1/2/3), and the p38 MAPKs (alpha, beta, gamma, delta) (Source: Kyriakis & Avruch, 2012, Physiological Reviews). These kinases are activated through a three-tier signaling cascade where a MAPK kinase kinase (MAPKKK) activates a MAPK kinase (MAPKK), which in turn phosphorylates and activates the MAPK (Source: Cargnello & Roux, 2011, Microbiology and Molecular Biology Reviews). Aberrant MAPK signaling is frequently implicated in human diseases, particularly cancer, where the ERK pathway is often constitutively active, and inflammatory diseases, where p38 and JNK pathways drive cytokine production (Source: Dhillon et al., 2007, Oncogene). Therapeutic strategies include the development of small-molecule inhibitors that target these kinases to block downstream signaling, though challenges such as pathway redundancy and feedback loops often lead to drug resistance (Source: Burotto et al., 2014, Cancer).

Other names

MAP kinasesMAPKsSerine/threonine-protein kinasesExtracellular signal-regulated kinases (ERK)c-Jun N-terminal kinases (JNK)p38 mitogen-activated protein kinases

Direct inhibition of kinase catalytic activity through ATP-competitive binding or allosteric modulation of the protein conformation (Source: PubMed).