Extracellular Signal-Regulated Kinases, Models of
Mitogen-activated protein (MAP) kinases consist of a family of protein kinases activated by a variety of cellular stimuli (Pearson et al. 2001). Four subfamilies of mammalian MAPK have been identified: ERK1 and ERK2: JNK; p38; and ERK5. Extracellular regulated kinase 1 and 2 (ERK1, ERK2), the original MAPK, was discovered as a kinase activity regulated by insulin. For a historical perspective on the discovery of the ERK cascade, see Blenis (1993). ERK1 and ERK2 (also known as p44 and p42 MAPK) signaling is key for the induction of synaptic plasticity and is essential for learning and memory (Thomas and Huganir 2004).
The core ERK signaling module consists of a three-tiered kinase cascade: the MAPKKK Raf1 or B-Raf that phosphorylates and activates the MAPKK MEK1/2 that in turn phosphorylates and activates the MAPK ERK1/2. The small G protein Ras activates Raf, the first kinase in the cascade. Activation of...
- Kuroda S, Schweighofer N et al (2001) Exploration of signal transduction pathways in cerebellar long-term depression by kinetic simulation. J Neurosci 21(15):5693–5702Google Scholar
- Song RS, Massenburg et al (2013) ERK regulation of phosphodiesterase 4 enhances dopamine-stimulated AMPA receptor membrane insertion. Proc Natl Acad Sci U S A. 110(38):15437–42Google Scholar
- Yoon S and Seger R (2006) The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions. Growth Factors 24(1):21–44Google Scholar
- Zhang Y, Liu RY et al (2012) Computational design of enhanced learning protocols. Nat Neurosci 15(2):294–297Google Scholar