Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes

J Exp Med. 1996 Oct 1;184(4):1365-75. doi: 10.1084/jem.184.4.1365.

Abstract

Integrin/ligand binding evokes tyrosine phosphorylation of various proteins. We reported previously that a 105 kD protein (pp105) was tyrosine phosphorylated by the engagement of beta 1 integrins in T lymphocytes. We show here that pp105 is a novel p130Cas (Crk-associated substrate)-related protein. Deduced amino acid sequence revealed that pp105 contains conserved motifs with p130Cas, and both pp105 and p130Cas bind to focal adhesion kinase (pp125FAK) and Crk. However, pp105 has a clearly distinct structure from p130Cas, and pp105 is preferentially expressed in lymphocytes, whereas p130Cas is expressed in adherent cells. With these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck, and SHPTP2 to pp105. These findings further define the roles of pp105/Cas-L and pp125FAK in the integrin-mediated signaling pathways.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Adhesion Molecules / metabolism*
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Integrin beta1 / metabolism*
  • Lymphocytes / physiology*
  • Molecular Sequence Data
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogene Proteins c-crk
  • RNA, Messenger / genetics
  • Rats
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Ubiquitin-Protein Ligases*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Crk protein, rat
  • DNA, Complementary
  • Integrin beta1
  • NEDD9 protein, human
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • RNA, Messenger
  • Recombinant Proteins
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, rat
  • CBL protein, human

Associated data

  • GENBANK/U64317