...Candy Laura Steffen; Pelin Kaya; Elisabeth Schaffner-Reckinger; Daniel Abankwa RAS drug development has made enormous strides in the past ten years, with the first direct KRAS inhibitor being approved in 2021. However, despite the clinical success of covalent KRAS-G12C inhibitors, we...

...Gabriela Bernal Astrain; Maya Nikolova; Matthew J. Smith RAS small GTPases regulate important signalling pathways and are notorious drivers of cancer development and progression. While most research to date has focused on understanding and addressing the oncogenic potential of three RAS oncogenes...

...Frazer A. Cook; Simon J. Cook The RAS-regulated RAF–MEK1/2–ERK1/2 pathway promotes cell proliferation and survival and RAS and BRAF proteins are commonly mutated in cancer. This has fuelled the development of small molecule kinase inhibitors including ATP-competitive RAF inhibitors. Type I and type...

...Swati Singh; Matthew J. Smith RAS GTPases are fundamental regulators of development and drivers of an extraordinary number of human cancers. RAS oncoproteins constitutively signal through downstream effector proteins, triggering cancer initiation, progression and metastasis. In the absence...

... since the majority of patients diagnosed with PDAC present with advanced unresectable disease, which is highly resistant to all forms of chemotherapy and radiotherapy. Activating mutations of an isoform of the RAS protein, KRAS, are found in almost all PDAC cases and occur during early stages...

...Soheila Rezaei Adariani; Marcel Buchholzer; Mohammad Akbarzadeh; Saeideh Nakhaei-Rad; Radovan Dvorsky; Mohammad Reza Ahmadian RAF (rapidly accelerated fibrosarcoma) Ser/Thr kinases (ARAF, BRAF, and CRAF) link the RAS (rat sarcoma) protein family with the MAPK (mitogen-activated protein kinase...

...Stephanie P. Mo; Judy M. Coulson; Ian A. Prior RAS proteins are small GTPases that regulate signalling networks that control cellular proliferation and survival. They are frequently mutated in cancer and a commonly occurring group of developmental disorders called RASopathies. We discuss recent...

...Atanu Chakraborty; Emily Linnane; Sarah Ross Oncogenic mutations in RAS genes underlie the pathogenesis of many human tumours, and there has been intense effort for over 30 years to develop effective and tolerated targeted therapeutics for patients with Ras-driven cancers. This review summarises...

...Ana Herrero; David Matallanas; Walter Kolch Nearly 30% of human tumours harbour mutations in RAS family members. Post-translational modifications and the localisation of RAS within subcellular compartments affect RAS interactions with regulator, effector and scaffolding proteins. New insights...

...-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) RAS The RAS–RAF–MEK1/2–ERK1/2 [where ERK is extracellular-signal-regulated kinase and MEK is MAPK (mitogen-activated protein kinase)/ERK kinase] signalling cascade controls the activity and/or expression...

...Sharon Eisenberg; Alex J. Laude; Alison J. Beckett; Craig J. Mageean; Veronica Aran; Maria Hernandez-Valladares; Yoav I. Henis; Ian A. Prior Ras GTPases are important regulators of pathways controlling proliferation, differentiation and transformation. Three ubiquitously expressed almost identical...

...Edita Aksamitiene; Anatoly Kiyatkin; Boris N. Kholodenko In the present paper, we describe multiple levels of cross-talk between the PI3K (phosphoinositide 3-kinase)/Akt and Ras/MAPK (mitogen-activated protein kinase) signalling pathways. Experimental data and computer simulations demonstrate...

...S. Yarwood; D. Bouyoucef-Cherchalli; P.J. Cullen; S. Kupzig Ras proteins are binary switches that, by cycling between inactive GDP-bound and active GTP-bound conformations, regulate multiple cellular signalling pathways including those that control cell growth, differentiation and survival...

...M.R. Philips Ras proteins associate with cellular membranes by virtue of a series of post-translational modifications of their C-terminal CAAX sequences. The discovery that two of the three enzymes that modify CAAX proteins are restricted to the endoplasmic reticulum led to the recognition that all...

... of the GDB–GTPase interaction. It is innate to the strong and specific interaction with the GTP-loaded GTPase, that GBDs will protect their partner GTPases from GAP (GTPase-activating protein) action. This feature is likely to cause an increase in cellular Ras-GTP levels, in particular in leucocytes...

...F. Chiaradonna; C. Magnani; E. Sacco; R. Manzoni; L. Alberghina; M. Vanoni Mutational activation of the ras gene is critical for the onset of different malignant phenotypes. We constructed a dominant negative mutant (GEF-DN) of a Ras activator protein (guanine nucleotide-exchange factor) that upon...

... of the Biochemical Society held at the University of Essex, Colchester, 2–4 July 2003 9 July 2003 © 2003 Biochemical Society 2003 apoptosis growth factor Mn superoxide dismutase Ras reactive oxygen species (ROS) senescence Abbreviations used: AP-1, activator protein-1; DPI...

... frequency varies according to the amplitude of the receptor stimuli. This suggests a requirement for molecular decoders, capable of interpreting such complex calcium signals into the correct physiological response. Ras proteins are binary molecular switches controlling a plethora of cellular responses...

... stress-activated protein kinases Ras senescence Aging and the Immune System 21 22 23 24 25 26 27 28 29 Palmero, I., Pantoja, C. and Semno. M. ( I 998) Nature (London) 395. I 25- I26 Zindy, F., Eischen. C. M., Randle. D. H., Karnijo, T., Cleveland, J. L.. Sherr, C. J. and Roussel. M. F. ( 1998) Genes...