Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates PI 3-kinase binding to T-cell antigen CTLA-4

Biochem Biophys Res Commun. 1998 Nov 9;252(1):14-9. doi: 10.1006/bbrc.1998.9559.

Abstract

CTLA-4 and CD28 are differentially expressed on T-cells. They bind to a common ligand B71/2 (CD80/86), however with different avidities. Unlike CD28 which augments the T-cell response, CTLA-4 operates predominately as a negative regulator of T-cell proliferation. The mechanism by which CTLA-4 can generate these intracellular signals is unclear. Little is known regarding the identity of the protein-tyrosine kinase(s) responsible for CTLA-4 phosphorylation and thus creating conditions for the reported binding to PI 3-kinase and the protein tyrosine phosphatase SHP-2. In this study, we demonstrate that Rlk (resting lymphocyte kinase) is capable of phosphorylating CTLA-4 at the YVKM motif. Consistent with this finding, Rlk is capable of providing conditions for the binding of the SH2 domains of PI 3-kinase to the receptor. CTLA-4 is therefore the first known substrate for Rlk suggesting the possibility that this kinase may participate in CTLA-4 function.

MeSH terms

  • Abatacept
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / chemistry
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • COS Cells
  • CTLA-4 Antigen
  • Homeostasis
  • Humans
  • Immunoconjugates*
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • Transfection

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Intracellular Signaling Peptides and Proteins
  • Recombinant Fusion Proteins
  • Abatacept
  • Phosphatidylinositol 3-Kinases
  • Tec protein-tyrosine kinase
  • Protein-Tyrosine Kinases
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases