Reactome: A Curated Pathway Database

Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530) [Homo sapiens]


Signaling by PI3K/AKT is frequently constitutively activated in cancer via gain-of-function mutations in one of the two PI3K subunits - PI3KCA (encoding the catalytic subunit p110alpha) or PIK3R1 (encoding the regulatory subunit p85alpha). Gain-of-function mutations activate PI3K signaling by diverse mechanisms. Mutations affecting the helical domain of PIK3CA and mutations affecting nSH2 and iSH2 domains of PIK3R1 impair inhibitory interactions between these two subunits while preserving their association. Mutations in the catalytic domain of PIK3CA enable the kinase to achieve an active conformation. PI3K complexes with gain-of-function mutations therefore produce PIP3 and activate downstream AKT in the absence of growth factors (Huang et al. 2007, Zhao et al. 2005, Miled et al. 2007, Horn et al. 2008, Sun et al. 2010, Jaiswal et al. 2009, Zhao and Vogt 2010, Urick et al. 2011).

Cross References
Database Identifier
BioModels Database BIOMD0000000175, BIOMD0000000477, BIOMD0000000137, BIOMD0000000424, BIOMD0000000255
Name Identifier Synonyms
cancer 162 [malignant tumor, malignant neoplasm, primary cancer]