Tyrosine kinases EnAbling adaptor molecules for chemokine-induced Rap1 activation in T cells

Sci Signal. 2012 Jul 31;5(235):pe33. doi: 10.1126/scisignal.2003383.

Abstract

Chemokines regulate T cell trafficking into secondary lymphoid organs and migration across endothelial cells in response to inflammatory signals. The small guanosine triphosphatase Rap1 is a critical regulator of chemokine signaling in T cells, but how chemokines activate Rap1 has been unclear. A study showed that Abl family tyrosine kinases were essential for chemokine-induced Rap1 activation, T cell polarization, and migration. Abl family kinases promoted Rap1 activation by phosphorylating the adaptor protein human enhancer of filamentation 1 (HEF1), thus establishing a critical Abl-HEF1-Rap1 signaling axis for chemokine-induced T cell migration.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Movement / immunology*
  • Chemokines / pharmacology*
  • Humans
  • Lymphocyte Activation / drug effects*
  • Models, Immunological
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • rap1 GTP-Binding Proteins / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Chemokines
  • NEDD9 protein, human
  • Phosphoproteins
  • ARG tyrosine kinase
  • Protein-Tyrosine Kinases
  • rap1 GTP-Binding Proteins