Naslov
MAP kinase signalling cascades in cell proliferation and apoptosis

Autori
Rumora, Lada ; Žanić Grubišić, Tihana

Vrsta, podvrsta i kategorija rada
Poglavlja u knjigama, znanstveni

Knjiga
Biochemistry and Immunology Intersections

Urednik/ci
Markotić, Anita ; Glavaš-Obrovac, Ljubica ; Varljen, Jadranka ; Žanić Grubišić, Tihana

Izdavač
Research Signpost

Grad
Lahti

Godina
2008

Raspon stranica
151-171

ISBN
978-81-308-0265-7

Ključne riječi
MAPK, apoptosis, proliferation

Sažetak
Mitogen -activated protein kinase (MAPK) signalling cascade is a highly conserved pathway implicated in diverse cellular functions, including proliferation, cell cycle arrest, migration, differentiation, senescence and apoptosis. A wide variety of extracellular stimuli, such as growth factors and environmental stresses, induce sequential phosphorylation and activation of MAPKs. MAPK pathways regulate eukariotic gene expression by playing structural adaptors and enzymatic activators in transcription complexes. MAPKs are serine/threonine kinases involved in transmitting signals from receptors on cell membrane to intracellular targets, such as elements of cytoskeleton, downstream kinases or nuclear transcription factors. In order to specify a MAPK substrate minimal recognition sequence (Ser/Thr-Pro), and additional docking domains are required. Classical D-domain is characterised by the presence of a cluster of basic residues followed by an LxL motif. The second type of docking domain represents a short peptide containing sequence FxF, located downstream from phosphoacceptor motif. There are three subfamilies of MAPKs: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNKs) and p38-MAPK. An additional “ big” MAPK, termed ERK5/BMK1, has been cloned. Each family member is activated by distinct pathway and transmits signals either independently or co-ordinately. MAPK signalling may either protect or enhance cell susceptibility to apoptosis depending on the cell type, stimuli, and the latency of activation of MAPKs. ERK1/2 is primarily involved in proliferation, transformation and differentiation, whereas JNK and p38 are activated in response to physiologic, osmotic or genotoxic stress, endotoxins, proinflammatory cytokines, and ultraviolet exposure and have the pro-apoptotic effects. Because of the similarity between ERK1/2 and ERK5 cascade, it has been proposed that ERK5 enhances cell growth and cell survival, rather than apoptosis. Although each member of MAPK superfamily is considered unique, they are only a part of the complex and interactive network of signalling pathways, and there is a complex cross talk and signal convergence among MAPK family members. The multiple downstream targets, cell type-, and cell cycle-specific molecular cross talks as well as different kinetics of activation, all are giving rise to the complexity of MAPK effects on cell death or survival. In this review, we will discuss recent developments in understanding how differential regulation and delicate balance between MAPKs signalling pathways contributes to the activation of apoptosis or cellular proliferation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA