The Phox homology (PX) domain, a new player in phosphoinositide signalling

Yue XU, Li-Fong SEET, Brendon HANSON, Wanjin HONG


Phosphoinositides are key regulators of diverse cellular processes. The pleckstrin homology (PH) domain mediates the action of PtdIns(3,4)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P3, while the FYVE domain relays the pulse of PtdIns3P. The recent establishment that the Phox homology (PX) domain interacts with PtdIns3P and other phosphoinositides suggests another mechanism by which phosphoinositides can regulate/integrate multiple cellular events via a spectrum of PX domain-containing proteins. Together with the recent discovery that the epsin N-terminal homologue (ENTH) domain interacts with PtdIns(4,5)P2, it is becoming clear that phosphoinositides regulate diverse cellular events through interactions with several distinct structural motifs present in many different proteins.

  • endosomes
  • membranes
  • phosphoinositide-binding domains
  • protein traffic
  • signal transduction


  • Abbreviations used: AP180, adaptor protein 180; ARF, ADP-ribosylation factor; ALK, activin-like receptor; ARNO, ARF nucleotide binding site opener; BTK, Bruton's tyrosine kinase; CALM, clathrin assembly lymphoid myeloid leukaemia protein; CISK, cytokine-independent survival kinase; CPY, carboxypeptidase Y; DPAP A, dipeptidyl aminopeptidase A; EEA1, early endosome autoantigen 1; EGF, epidermal growth factor; ENTH, epsin N-terminal homologue; FANCA, Fanconi anaemia protein A; GAP, GTPase-activating protein; GEF, guanine nucleotide exhange factor; GFP, green fluorescent protein; GRP1, general receptor for phosphoinositides-1; HIP, huntingtin interacting protein; Hrs, hepatocyte growth factor-regulated tyrosine kinase substrate; HS1, haemopoietic-specific protein 1; HS1BP3, HS1 SH3 domain binding protein; IL, interleukin; I-1 RCP, imidazoline-1 receptor candidate protein; MAP, mitogen-activated protein; MDC protein, metalloprotease, disintegrin, cysteine-rich protein; MTM1, myotubularin; MTMR, myotubularin-related protein; PDGF, platelet-derived growth factor; PDK1, phoshoinositide-dependent kinase 1; PH, pleckstrin homology; PI, phosphoinositide; PI3Ks, PtdIns 3-kinases; PI4Ks, PtdIns 4-kinases; PI5Ks, PtdIns 5-kinases; PIP, phosphatidylinositol phosphate; PIPK, PIP kinase; PITPs, PtdIns transfer proteins; PKB, protein kinase B; PLC, phospholipase C; PLD, phospholipase D; PX, Phox homology; PXA, PX domain-associated; PXK, PX domain-containing protein kinase; SARA, Smad anchor for receptor activation; SM domain, SNX1–Mvp1p domain; SDPs, SM domain proteins; SH, Src homology; SHIP, SH2 domain-containing inositol 5-phosphatase; SKIP, skeletal muscle and kidney-enriched 5-inositol phosphatase; SNARE, soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor; SNX, sorting nexin; TGF, transforming growth factor; VHS, Vps27p/Hrs/Stam.