The MAPK signaling cascade

Abstract

The transmission of extracellular signals into their intracellular targets is mediated by a network of interacting proteins that regulate a large number of cellular processes. Cumulative efforts from many laboratories over the past decade have allowed the elucidation of one such signaling mechanism, which involves activations of several membranal signaling molecules followed by a sequential stimulation of several cytoplasmic protein kinases collectively known as mitogen-activated protein kinase (MAPK) signaling cascade. Up to six tiers in this cascade contribute to the amplification and specificity of the transmitted signals that eventually activate several regulatory molecules in the cytoplasm and in the nucleus to initiate cellular processes such as proliferation, differentiation, and development. Moreover, because many oncogenes have been shown to encode proteins that transmit mitogenic signals upstream of this cascade, the MAPK pathway provides a simple unifying explanation for the mechanism of action of most, if not all, nonnuclear oncogenes. The pattern of MAPK cascade is not restricted to growth factor signaling and it is now known that signaling pathways initiated by phorbol esters, ionophors, heat shock, and ligands for seven transmembrane receptors use distinct MAPK cascades with little or no cross-reactivity between them. In this review we emphasize primarily the first MAPK cascade to be discovered that uses the MEK and ERK isoforms and describe their involvement in different cellular processes.

Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

“…The presence of activated MEK and ERK on cytoskeletal structures and their association with focal adhesions and microtubules is consistent with the hypothesis that localized MAPK signaling modulates Rho signaling [89][90][91][92][93][94][95]. Indeed, considerable evidence indicates that the integration of Rho family GTPase and ERK signaling is important in the control of cell morphogenesis [96][97][98][99][100][101][102][103].…”

ERK/pERK expression and B-raf mutations in colon adenocarcinomas: correlation with clinicopathological characteristics

“…Deregulation of the MAPK signalling pathway has often been associated with oncogenic transformation [24]. In this regard, there is accumulating evidence involving ERK activation in the tumorigenesis of various human cancers such as prostate, breast, colon and ovary [25-29].…”

Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis

“…These kinases build the end of an intracellular pathway involving multiple serine/threonine kinases that are activated in a cascade, including mitogen-activated kinase kinase (MEK). 24 The phosphorylated forms of MAPK 1 and 2 were both increased in retinal protein lysates of Epo-treated animals compared with vehicle-treated controls (Figure 3b). Again, the expression of the unphosphorylated proteins was unaffected under Epo application.…”