PI3 kinase signalling has been associated with the development and progression of many cancer types including colorectal cancer (CRC). The two most commonly mutated genes and key regulators of PI3K signalling are PIK3CA and PTEN. Cross-talk between PI3K and MAPK pathways through KRAS has also been implicated in tumourgenesis. We have explored the interplay between PI3K and MAPK signalling on a panel of 12 colorectal cancer cell lines stratified by their mutation status in key regulatory genes. Using GST-tagged GRP1PH and immunofluorescence microscopy, PI(3,4,5)P3 formation at the cell membrane was monitored over an EGF stimulation timecourse. Reverse Phase Protein Array (RPPA) comprising of 133 antibodies was also conducted on the EGF stimulated cell line panel, to assess the regulation of downstream proteins as well as the phosphorylation state of selected proteins. In doing so, we have begun to dissect the differences in signalling between exon 9 and exon 20 PIK3CA mutations and the contribution KRAS has to this pathway.