description
Phosphatidylinositol-5-phosphate (PI5P) may modulate PI3K/AKT signaling in several ways. PI5P is used as a substrate for production of phosphatidylinositol-4,5-bisphosphate, PI(4,5)P2 (Rameh et al. 1997, Clarke et al. 2008, Clarke et al. 2010, Clarke and Irvine 2013, Clarke et al. 2015), which serves as a substrate for activated PI3K, resulting in the production of PIP3 (Mandelker et al. 2009, Burke et al. 2011). The majority of PI(4,5)P2 in the cell, however, is produced from the phosphatidylinositol-4-phosphate (PI4P) substrate (Zhang et al. 1997, Di Paolo et al. 2002, Oude Weernink et al. 2004, Halstead et al. 2006, Oude Weernink et al. 2007). PIP3 is necessary for the activating phosphorylation of AKT. AKT1 can be deactivated by the protein phosphatase 2A (PP2A) complex that contains a regulatory subunit B56-beta (PPP2R5B) or B56-gamma (PPP2R5C). PI5P inhibits AKT1 dephosphorylation by PP2A through an unknown mechanism (Ramel et al. 2009). Increased PI5P levels correlate with inhibitory phosphorylation(s) of the PP2A complex. MAPK1 (ERK2) and MAPK3 (ERK1) are involved in inhibitory phosphorylation of PP2A, in a process that involves IER3 (IEX-1) (Letourneux et al. 2006, Rocher et al. 2007). It is uncertain, however, whether PI5P is in any way involved in ERK-mediated phosphorylation of PP2A or if it regulates another PP2A kinase

external resources
NCBI:1383020
REACTOME:R-HSA-6811558
PUBMED:12422219
PUBMED:16979564
PUBMED:19805105
PUBMED:17200115
PUBMED:21827948
PUBMED:19576174
PUBMED:18753295
PUBMED:19896968
PUBMED:16456541
PUBMED:25495341
PUBMED:15464023
PUBMED:23758345
PUBMED:9367159
PUBMED:9211928
PUBMED:17245604

genes
AKT1 , BTC , CD19 , CD28 , CD80 , CD86 , HBEGF , EGF , EGFR , ERBB2 , ERBB3 , ERBB4 , EREG , FGF1 , FGF2 , FGF3 , FGF4 , FGF5 , FGF6 , FGF7 , FGF8 , FGF9 , FGF10 , FGFR1 , FGFR3 , FGFR2 , FGFR4 , FYN , GAB1 , GRB2 , HGF , NRG1 , INS , INSR , IRS1 , KIT , LCK , MET , KITLG , PDGFA , PDGFB , PDGFRA , PDGFRB , PIK3CA , PIK3CB , PIK3CD , PIK3R1 , PIK3R2 , PIP4K2A , PPP2CA , PPP2CB , PPP2R1A , PPP2R1B , PPP2R5A , PPP2R5B , PPP2R5C , PPP2R5D , PPP2R5E , MAPK1 , MAPK3 , PTPN11 , SRC , VAV1 , FGF23 , PIP5K1A , PIP5K1B , PIP4K2B , PIK3R3 , IRS2 , FGF18 , FGF17 , FGF16 , IER3 , KL , NRG2 , FGF19 , NRG3 , FRS2 , PIP5K1C , FGF20 , FGF22 , ICOS , TRAT1 , PIP4K2C , PIK3AP1 , NRG4 , KLB ,