Ras and PI3K Signaling Pathways in Cancer

  • Falconieri_cancer_Ras_PI3K_pathways-01

Ras and PI3K (p85/p110) are two signaling pathways downstream of growth factor receptors (EGFR here) that can enhance cell survival. Mutations can lead to the hyperactivity of these pathways, and allow cancer cells to survive abnormally and outgrow their normal neighbors.

This illustration, designed for a review article, depicts the PI3K (blue) and Ras (orange) pathways using human protein structures where available.  Gray circles indicate proteins that form a complex to propagate a signal (EGFR, SOS, SHC, GRB2 activate Ras, and EGFR, p85, and p110 activate PIP3 signaling).

This piece was created with Cinema4D, embedded Python Molecular Viewer (ePMV), Adobe Photoshop, and Illustrator.

Structure References
All structures shown are of human proteins. If a structure of > 75% of the full length human protein was not available, the protein is shown as a circle proportional to its estimated mass, indicated in kilodaltons (kDa).

EGFR (UniProt P00533): PDB 1YY9 (extracellular domain), PDB 2M20 (membrane domain), PDB 4ZSE (intracellular domain)

PI3K Pathway

PI3K complex:

p110/PK3CA (Uniprot P42336): PDB 2RD0
p85/PIK3R1 (Uniprot P27986): ~80 kDa

PTEN (Uniprot P60484): PDB 5BZZ
AKT1 (Uniprot P31749): PDB 4EJN
mTOR (Uniprot P42345): PDB 5FLC
PDK1 (Uniprot O15530): ~61 kDa
MDM2 (Uniprot Q00987): ~54 kDa
FKHR (Uniprot Q12778): ~72 kDa
BAD (Uniprot Q92934): ~18 kDa
NFkB (Uniprot P19838): PDB 1SVC
GSK3β (Uniprot P49841): PDB 1J1B
TSC complex:
TSC1/hamartin (Uniprot Q92574): ~128 kDa
TSC2/tuberin (Uniprot P49815): ~198 kDa

Ras Pathway

Ras/Kras (UniProt – P01116): PDB 4LDJ (GDP-bound), PDB 4DSO (GTP-bound)

SHC, SOS, GRB2 complex:

SHC (Uniprot P29353 ): ~64 kDA
GRB2 (Uniprot P62993): PDB 1GRI
SOS (Uniprot Q07889): PDB 3KSY

NF1 (Uniprot P21359): ~312 kDa
RAF1 (Uniprot P04049): ~71 kDa
BRAF (Uniprot P15056): ~84 kDa
MEK (Uniprot Q02750): PDB 3EQD
ERK (Uniprot P27361): PDB 2ZOQ