The phosphoinositide-3-OH kinase (PI3K) signalling regulates various cellular processes, including cell survival, growth, proliferation and motility, and is among the most frequently mutated pathway in cancer. It has been identified a serine (at codon 83) adjacent to N-terminus SH3 domain in the PI3K regulatory subunit p85αPI3K, that is phosphorylated by Protein Kinase A (PKA) in vivo and in vitro. Virtually, all receptors binding p85αPI3K can cooperate with cAMP–PKA signals via phosphorylation of p85αPI3KSer83. To analyse the role of p85αPI3KSer83 in Retinoic Acid (RA) and cAMP signalling in MCF7 cells, p85αPI3K mutated forms were used, in which Ser83 has been substituted with alanine (p85A) to prevent phosphorylation or with aspartic acid (p85D) to mimic the phosphorylated residue. This study points p85αPI3KSer83 out as the physical link between different pathways (cAMP-PKA, RA and FAK) and as an important regulator of MCF7 cells proliferation and migration.