Table 1.

Members of the p38 mitogen-activated protein kinase (MAPK) subfamily.

p38 Subfamily	Other Names	Upstream	Location/Function	Dysfunction and Diseases
p38α	MAPK14, SAPK2a, CSBP	MKK3, MKK4, MKK6, MKK7	Ubiquitously expressed at significant levels in most cell types. Involved in the regulation of cell proliferation, differentiation, development, and response to stress [77,78,84,99].	Defective placental angiogenesis causing embryo death (mouse), symmetric synchronous cell cleavage (zebrafish), reduction in erythropoietin (Epo) production [99], leading to anemia, the impairment of glucogenesis (mice), and lipid-induced insulin-resistance (rat) [77,97].
p38β	MAPK 11	MKK3, MKK4, MKK6	Ubiquitously expressed; upregulated in the CNS and lungs, downregulated in the healthy heart [104,105,106].	No phenotype found [77].
p38γ	MAPK 13, ERK6, SAPK3 1	MKK3, MKK4, MKK6MKK7	Myoblast and skeletal muscle./(1) Under stress conditions, they act on scaffold proteins targeting the plasma membrane cytoskeleton at sites of neuromuscular junctions and gap junctions [107]. (2) Recent studies indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes via the activation of p38γ/p62/ mTORC1 [89].	No phenotype found (mouse) [77]. Meiotic G2/M progression of oocytes (xenopus) [77,104,105].
p38δ	MAPK 12, SAPK4	MKK3, MKK4, MKK6, MKK7	Only expressed in the lungs, kidney, testis, spleen, pancreas, and small intestine in humans, rats, and mice, but not in other vertebrates; enriched in endocrine glands [107,108]./(1) Regulates cytoplasmic microtubule dynamics, including tau protein [107]. (2) Upregulated in the liver in obese patients with NAFLD [89].	No phenotype found [77].

SAPK: stress-activated protein kinase; CNS: central nervous system; mTORC1: mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1; NAFLD: nonalcoholic fatty liver disease.