Map kinase pathways are essential for cell signaling in eukaryotes, regulating processes like cell proliferation, differentiation, and death. These pathways consist of three sequentially activated protein kinases: mapkkk, mapkk, and mapk. The mapkkk is typically activated by interactions with a small gtpase or phosphorylation by protein kinases downstream from cell surface receptors. The mapkk then activates the mapk through dual phosphorylation of a conserved tripeptide txy motif. Once activated, the mapk phosphorylates various substrates in the cytosol and nucleus, leading to changes in protein function and gene expression that execute the appropriate biological response. map kinases are grouped into three main families: erk, jnk, and p38/sapk. erk family members possess a tey motif in the activation segment and can be subdivided into two groups: classic erk1/2 and larger erk5. the classic erk1/2 module responds primarily to growth factors and mitogens to induce cell growth and differentiation. important upstream regulators include cell surface receptors, such as receptor tyrosine kinases, g-protein-coupled receptors, and integrins, as well as the small gtpases ras and rap. the mapkks for the classic erk1/2 module are mek1 and mek2, and the mapkkks include members of the Raf family, mos, and tpl2. jnk family members contain a tpy motif in the activation segment and include jnk1, jnk2, and jnk3. the jnk module is activated by environmental stresses and inflammatory cytokines, as well as growth factors. the jnk module plays an important role in apoptosis, inflammation, cytokine production, and metabolism. the mapkks for the jnk module are mkk4 and mkk7, and the mapkkks include mekk1 and mekk4, mlk2 and mlk3, ask1, tak1, and tpl2. p38 family members possess a tgy motif in the activation segment and include p38α, p38β, p38γ, and p38δ. like jnk modules, p38 modules are strongly activated by environmental stresses and inflammatory cytokines. p38 activation contributes to inflammation, apoptosis, cell differentiation, and cell cycle regulation. the primary mapkks for p38 modules are mkk3 and mkk6, and the mapkkks include mlk2 and mlk3, mekk, ask, tak1, and tao1 and tao2. important substrates in p38 signaling include the downstream kinases mk2/3, prak, and msk1 and msk2, as well as various transcription factors.Map kinase pathways are essential for cell signaling in eukaryotes, regulating processes like cell proliferation, differentiation, and death. These pathways consist of three sequentially activated protein kinases: mapkkk, mapkk, and mapk. The mapkkk is typically activated by interactions with a small gtpase or phosphorylation by protein kinases downstream from cell surface receptors. The mapkk then activates the mapk through dual phosphorylation of a conserved tripeptide txy motif. Once activated, the mapk phosphorylates various substrates in the cytosol and nucleus, leading to changes in protein function and gene expression that execute the appropriate biological response. map kinases are grouped into three main families: erk, jnk, and p38/sapk. erk family members possess a tey motif in the activation segment and can be subdivided into two groups: classic erk1/2 and larger erk5. the classic erk1/2 module responds primarily to growth factors and mitogens to induce cell growth and differentiation. important upstream regulators include cell surface receptors, such as receptor tyrosine kinases, g-protein-coupled receptors, and integrins, as well as the small gtpases ras and rap. the mapkks for the classic erk1/2 module are mek1 and mek2, and the mapkkks include members of the Raf family, mos, and tpl2. jnk family members contain a tpy motif in the activation segment and include jnk1, jnk2, and jnk3. the jnk module is activated by environmental stresses and inflammatory cytokines, as well as growth factors. the jnk module plays an important role in apoptosis, inflammation, cytokine production, and metabolism. the mapkks for the jnk module are mkk4 and mkk7, and the mapkkks include mekk1 and mekk4, mlk2 and mlk3, ask1, tak1, and tpl2. p38 family members possess a tgy motif in the activation segment and include p38α, p38β, p38γ, and p38δ. like jnk modules, p38 modules are strongly activated by environmental stresses and inflammatory cytokines. p38 activation contributes to inflammation, apoptosis, cell differentiation, and cell cycle regulation. the primary mapkks for p38 modules are mkk3 and mkk6, and the mapkkks include mlk2 and mlk3, mekk, ask, tak1, and tao1 and tao2. important substrates in p38 signaling include the downstream kinases mk2/3, prak, and msk1 and msk2, as well as various transcription factors.