RGS-PX1, a GAP for GalphaS and sorting nexin in vesicular trafficking

Science. 2001 Nov 30;294(5548):1939-42. doi: 10.1126/science.1064757.

Abstract

Heterotrimeric GTP-binding proteins (G proteins) control cellular functions by transducing signals from the outside to the inside of cells. Regulator of G protein signaling (RGS) proteins are key modulators of the amplitude and duration of G protein-mediated signaling through their ability to serve as guanosine triphosphatase-activating proteins (GAPs). We have identified RGS-PX1, a Galpha(s)-specific GAP. The RGS domain of RGS-PX1 specifically interacted with Galpha(s), accelerated its GTP hydrolysis, and attenuated Galpha(s)-mediated signaling. RGS-PX1 also contains a Phox (PX) domain that resembles those in sorting nexin (SNX) proteins. Expression of RGS-PX1 delayed lysosomal degradation of the EGF receptor. Because of its bifunctional role as both a GAP and a SNX, RGS-PX1 may link heterotrimeric G protein signaling and vesicular trafficking.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cattle
  • Cell Line
  • Cyclic AMP / metabolism
  • Endosomes / chemistry
  • Endosomes / metabolism
  • ErbB Receptors / metabolism
  • GTP-Binding Protein alpha Subunits, Gs / antagonists & inhibitors
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / metabolism*
  • Guanosine Triphosphate / metabolism
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Protein Transport
  • RGS Proteins / chemistry
  • RGS Proteins / metabolism*
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Sorting Nexins
  • Substrate Specificity
  • Vesicular Transport Proteins*

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Carrier Proteins
  • GTPase-Activating Proteins
  • RGS Proteins
  • Receptors, Adrenergic, beta-2
  • SNX13 protein, human
  • Sorting Nexins
  • Vesicular Transport Proteins
  • Guanosine Triphosphate
  • Cyclic AMP
  • ErbB Receptors
  • Mitogen-Activated Protein Kinases
  • GTP-Binding Protein alpha Subunits, Gs