The second messenger phosphatidylinositol 3,4,5-trisphosphate
(PIP3, PtdIns(3,4,5)P) is generated by the action of phosphoinositide
3-kinase (PI3K) in response to growth factors and insulin and regulates a range of cellular processes. Proteins containing the plekstrin homology (PH) domain can interact specifically with PIP3 or its immediate breakdown product, phosphatidylinositol 3,4-diphosphate (PIP2, PtdIns(3,4)P). Proteins with a PH domain have also been found to bind to PIs other than PIP3 or PIP2. Pleckstrin homology domain-containing family A member 4 (PLEKHA4 aka PEPP1) is able to specifically bind phosphatidylinositol 3-phosphate (PI3P) but not other phosphoinositides (Dowler et al. 2000). Two related isoforms of
PLEKHA4, PLEKHA5 and 6 (PEPP2 and PEPP3), possess a very similar PH domain sequence, indicating that they may also interact with PI3P (Dowler et al. 2000, Yamada et al. 2012). These proteins may function as adaptor molecules since they possess no obvious catalytic moieties.