Cell proliferation and many other cell processes can be regulated through a signaling pathway that involves an enzyme called PI3K. This ‘heterodimeric’ enzyme is made up of two protein subunits, one of which is called p85α and inhibits the other subunit of the enzyme (known as p110) to prevent uncontrolled cell proliferation. Activation of the class 1A PI3K is gated, in part, by the p85α regulatory subunit, which contains a Src homology 3 (SH3) domain, two proline-rich (PR) regions (PR1 and PR2) separated by a Rho-GAP/BCR-homology (BH) domain, and two Src homology 2 (SH2) domains (nSH2, cSH2) flanking an inter-SH2 (iSH2) domain [PMID: 26222500].
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