MAP kinases (CMGC kinases) may be divided into three major families: ERK, JNK and p38 MAP kinases.

ERK may be activated by phosphorylation by the dual specificity mitogen-activated kinase kinases, MAP2K1 (Q02750, also known as MEK1) and MAP2K2 (P36507, also known as MEK2). The inhibitors PD98059 [1,3] and U0126 [4-5] act to inhibit these enzymes [2], and are used to inhibit ERK1 and ERK2.

JNK may be activated by phosphorylation by the dual specificity mitogen-activated kinase kinases, MAP2K4 (P45985, also known as JNKK1) and MAP2K7 (O14733, also known as JNKK2) .

p38 may be activated by phosphorylation by the dual specificity mitogen-activated kinase kinases, MAP2K3 (P46734, also known as MEK3) and MAP2K6 (P52564, also known as SAPKK3).

1. Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR. (1995) PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem, 270 (46): 27489-94. [PMID:7499206]

2. Davies SP, Reddy H, Caivano M, Cohen P. (2000) Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J, 351 (Pt 1): 95-105. [PMID:10998351]

3. Dudley DT, Pang L, Decker SJ, Bridges AJ, Saltiel AR. (1995) A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA, 92 (17): 7686-9. [PMID:7644477]

4. Duncia JV, Santella JB, Higley CA, Pitts WJ, Wityak J, Frietze WE, Rankin FW, Sun JH, Earl RA, Tabaka AC et al.. (1998) MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorg Med Chem Lett, 8 (20): 2839-44. [PMID:9873633]

5. Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F et al.. (1998) Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem, 273 (29): 18623-32. [PMID:9660836]