ACAP4 interacts with CrkII to promote the recycling of integrin β1

Biochem Biophys Res Commun. 2019 Aug 13;516(1):8-14. doi: 10.1016/j.bbrc.2019.05.173. Epub 2019 Jun 8.

Abstract

ACAP4, a GTPase-activating protein (GAP) for the ADP-ribosylation factor 6 (ARF6), plays import roles in cell migration, cell polarity, vesicle trafficking and tumorigenesis. Similarly, the ubiquitously expressed adaptor protein CrkII functions in a wide range of cellular activities, including cell proliferation, T cell adhesion and activation, tumorigenesis, and bacterial pathogenesis. Here, we demonstrate that ACAP4 physically interacts with CrkII. Biochemical experiments revealed that ACAP4550-660 and the SH3N domain of CrkII are responsible for the interaction. Functional characterization showed that the interaction is required for the recruitment of ACAP4 to the plasma membrane where ACAP4 functions to regulate the recycling of the signal transducer integrin β1. Thus, we suggest that the CrkII-ACAP4 complex may be involved in regulation of cell adhesion.

Keywords: ACAP4; Cell adhesion; CrkII; Integrin β1; Recycling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 6
  • Cell Adhesion
  • Cell Membrane / metabolism
  • GTPase-Activating Proteins / analysis
  • GTPase-Activating Proteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Integrin beta1 / analysis
  • Integrin beta1 / metabolism*
  • Protein Interaction Domains and Motifs
  • Protein Interaction Maps*
  • Protein Transport
  • Proto-Oncogene Proteins c-crk / analysis
  • Proto-Oncogene Proteins c-crk / metabolism*

Substances

  • ADP-Ribosylation Factor 6
  • GTPase-Activating Proteins
  • Integrin beta1
  • Proto-Oncogene Proteins c-crk
  • ASAP3 protein, human
  • ARF6 protein, human