Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design

JML Ostrem, KM Shokat - Nature reviews Drug discovery, 2016 - nature.com
KRAS is the most frequently mutated oncogene in human cancer. In addition to holding this
distinction, unsuccessful attempts to target this protein have led to the characterization of …

G protein mechanisms: insights from structural analysis

SR Sprang - Annual review of biochemistry, 1997 - annualreviews.org
This review is concerned with the structures and mechanisms of a superfamily of regulatory
GTP hydrolases (G proteins). G proteins include Ras and its close homologs, translation …

K-Ras (G12C) inhibitors allosterically control GTP affinity and effector interactions

JM Ostrem, U Peters, ML Sos, JA Wells, KM Shokat - Nature, 2013 - nature.com
Somatic mutations in the small GTPase K-Ras are the most common activating lesions found
in human cancer, and are generally associated with poor response to standard therapies …

[HTML][HTML] Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1

L Bar-Peled, LD Schweitzer, R Zoncu, DM Sabatini - Cell, 2012 - cell.com
Summary The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to
numerous cues, including amino acids, which promote mTORC1 translocation to the …

The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1

ZY Tsun, L Bar-Peled, L Chantranupong, R Zoncu… - Molecular cell, 2013 - cell.com
The mTORC1 kinase is a master growth regulator that senses numerous environmental
cues, including amino acids. The Rag GTPases interact with mTORC1 and signal amino …

Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma

J Okosun, RL Wolfson, J Wang, S Araf, L Wilkins… - Nature …, 2016 - nature.com
Follicular lymphoma is an incurable B cell malignancy characterized by the t (14; 18)
translocation and mutations affecting the epigenome,. Although frequent gene mutations in …

Rab 7: an important regulator of late endocytic membrane traffic.

Y Feng, B Press, A Wandinger-Ness - The Journal of cell biology, 1995 - rupress.org
Rab5 and rab7 proteins belong to a superfamily of small molecular weight GTPases known
to be associated with early and late endosomes, respectively. The rab5 protein plays an …

Small-molecule modulation of Ras signaling

J Spiegel, PM Cromm, G Zimmermann… - Nature chemical …, 2014 - nature.com
Despite intense efforts in pharmaceutical industry and academia, a therapeutic grip on
oncogenic Ras proteins has remained elusive. Mutated Ras is associated with∼ 20− 30% of …

Ras and Rap1: A tale of two GTPases

S Shah, EJ Brock, K Ji, RR Mattingly - Seminars in cancer biology, 2019 - Elsevier
Ras oncoproteins play pivotal roles in both the development and maintenance of many
tumor types. Unfortunately, these proteins are difficult to directly target using traditional …

Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation

DR Ambruso, C Knall, AN Abell… - Proceedings of the …, 2000 - National Acad Sciences
A 5-week-old male infant presented with severe bacterial infections and poor wound
healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased …