TY - JOUR
T1 - Somatic mutations in PI3Kα
T2 - Structural basis for enzyme activation and drug design
AU - Gabelli, Sandra B.
AU - Mandelker, Diana
AU - Schmidt-Kittler, Oleg
AU - Vogelstein, Bert
AU - Amzel, L. Mario
N1 - Funding Information:
Support was provided by the Virginia and D.K. Ludwig Fund for Center Research and National Institutes of Health Grants CA43460 , GM07309 , and GM07184 .
PY - 2010/3
Y1 - 2010/3
N2 - The PI3K pathway is a communication hub coordinating critical cell functions including cell survival, cell growth, proliferation, motility and metabolism. Because PI3Kα harbors recurrent somatic mutations resulting in gains of function in human cancers, it has emerged as an important drug target for many types of solid tumors. Various PI3K isoforms are also being evaluated as potential therapeutic targets for inflammation, heart disease, and hematological malignancies. Structural biology is providing insights into the flexibility of the PI3Ks, and providing basis for understanding the effects of mutations, drug resistance and specificity.
AB - The PI3K pathway is a communication hub coordinating critical cell functions including cell survival, cell growth, proliferation, motility and metabolism. Because PI3Kα harbors recurrent somatic mutations resulting in gains of function in human cancers, it has emerged as an important drug target for many types of solid tumors. Various PI3K isoforms are also being evaluated as potential therapeutic targets for inflammation, heart disease, and hematological malignancies. Structural biology is providing insights into the flexibility of the PI3Ks, and providing basis for understanding the effects of mutations, drug resistance and specificity.
KW - Gain of function
KW - H1047R mutant
KW - PI3K
KW - Somatic mutation
KW - p110/p85
UR - http://www.scopus.com/inward/record.url?scp=75349088737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75349088737&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2009.11.020
DO - 10.1016/j.bbapap.2009.11.020
M3 - Review article
C2 - 19962457
AN - SCOPUS:75349088737
SN - 1570-9639
VL - 1804
SP - 533
EP - 540
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 3
ER -