Mitogen-activated protein kinase pathways

Robinson, Megan J.; Cobb, Melanie H.

doi:10.1016/s0955-0674(97)80061-0

Cited by 2,309 publications

(1,420 citation statements)

References 80 publications

Supporting

Mentioning

1,388

Contrasting

Unclassified

Order By: Relevance

“…Once phosphorylated, ERKs lose their affinity for these partners and undergo a rapid relocalization to nucleus, where they phosphorylate multiple nuclear proteins. In the nucleus, ERKs perform essential functions that regulate transcription, DNA replication, chromatin remodeling, and miRNA synthesis [60,61] among others. However, ERKs extranuclear component is just as important.…”

Section: Some Space For Erksmentioning

confidence: 99%

The Ras‐ERK pathway: Understanding site‐specific signaling provides hope of new anti‐tumor therapies

2010

View full text Add to dashboard Cite

Recent discoveries have suggested the concept that intracellular signals are the sum of multiple, site-specified subsignals, rather than single, homogeneous entities. In the context of cancer, searching for compounds that selectively block subsignals essential for tumor progression, but not those regulating ''house-keeping'' functions, could help in producing drugs with reduced side effects compared to compounds that block signaling completely. The Ras-ERK pathway has become a paradigm of how space can differentially shape signaling. Today, we know that Ras proteins are found in different plasma membrane microdomains and endomembranes. At these localizations, Ras is subject to site-specific regulatory mechanisms, distinctively engaging effector pathways and switching-on diverse genetic programs to generate different biological responses. The Ras effector pathway leading to ERKs activation is also under strict, space-related regulatory processes. These findings may open a gate for aiming at the Ras-ERK pathway in a spatially restricted fashion, in our quest for new anti-tumor therapies.

show abstract

Section: Some Space For Erksmentioning

confidence: 99%

The Ras‐ERK pathway: Understanding site‐specific signaling provides hope of new anti‐tumor therapies

2010

View full text Add to dashboard Cite

show abstract

“…In mammals, three major mitogen-activated protein kinase (MAPK) families that differ in their substrate specificity and responses to stress have been identified and have been implicated in the pathogenesis of inflammatory diseases such as asthma: c-Jun-N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase (for review, Robinson & Cobb, 1997;Ip & Davis, 1998). The JNK group is activated by exposure of cells to cytokines and to environmental stress (for review, Whitmarsh & Davis, 1996).…”

Section: Introductionmentioning

confidence: 99%

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Eynott

Nath

Leung

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

1 Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N-terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)-1. 2 We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9-cd] pyrazole-6 (2 H)-one), in a model of chronic allergic inflammation in the rat. 3 Rats sensitised to ovalbumin (OA) were exposed to OA-aerosol every third day on six occasions and were treated with SP600125 (30 mg kg À1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T-cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine. 4 SP600125 significantly reduced the number of eosinophils (Po0.05) and lymphocytes (Po0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (Po0.05) and CD 2 þ T-cell (Po0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (Po0.05) and epithelial cell incorporation (Po0.05). 5 SP600125 did not alter bronchial hyper-responsiveness observed after chronic allergen exposure. 6 Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.

show abstract

“…18 BRAF represent one type of RAF serine/threonine kinases that play a central role in the transduction of signals along the RAS-RAF-MAPK pathway regulat-ing cell growth, differentiation, and apoptosis in response to cytokines, hormones, and growth factors. 19 This major genetic alteration involved in the pathogenesis of PTC is an activating mutation of the BRAF gene occurring in about 45% of the sporadic type (reviewed by Xing 20 ) resulting in increased kinase activity of BRAF with activation of ERK. BRAF-activating missense point mutations in the kinase domain are clustered in exons 11 and 15 of the gene.…”

mentioning

confidence: 99%

Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements

et al. 2007

View full text Add to dashboard Cite

Diffuse sclerosing variant of papillary thyroid carcinoma (PTC) is a rare tumour with a characteristic morphology as well as a strong preponderance for younger female patients. The T1799A missense mutation in exon 15 of the BRAF gene and RET/PTC rearrangement have been identified as the dominant genetic tumour initiation events in the pathogenesis of PTC leading to a constitutive activation of the RAS-RAF-MAPK pathway. In order to elucidate the pathogenesis of diffuse sclerosing variant of PTC, the prevalence of BRAF mutation and RET/PTC were determined by RT-polymerase chain reaction and DNA-sequence analysis in tumour samples of seven patients with this variant (all female, age range 15-61 years, mean 33.3 years) without prior radiation exposure. None of these cases showed a BRAF mutation. RET/PTC1 (two out of seven) and RET/PTC3 (one out of seven), which have been shown in large PTC series to comprise together more than 90% of RET/PTC types, were found in o50% of the cases investigated. All seven samples expressed the RET tyrosine kinase domain but lacked its extracellular domain potentially suggesting the existence of rare types of RET/PTC rearrangement in the four remained cases of diffuse sclerosing variant of PTC. Regarding this subtype, our study confirmed the paradigm of a mutual exclusivity between RET/PTC and BRAF in PTC. Additionally, this rare variant of papillary thyroid carcinoma may represent a tumour type susceptible to RET-targeted therapies.

show abstract

Mitogen-activated protein kinase pathways

Cited by 2,309 publications

References 80 publications

The Ras‐ERK pathway: Understanding site‐specific signaling provides hope of new anti‐tumor therapies

The Ras‐ERK pathway: Understanding site‐specific signaling provides hope of new anti‐tumor therapies

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements

Contact Info

Product

Resources

About