Restoration of thymocyte development and function in zap-70-/- mice by the Syk protein tyrosine kinase

Immunity. 1997 Sep;7(3):369-77. doi: 10.1016/s1074-7613(00)80358-1.

Abstract

The Syk family of protein tyrosine kinases, consisting of ZAP-70 and Syk, associate with the pre- and alphabeta T cell antigen receptors (TCRs) and undergo tyrosine phosphorylation and activation following receptor engagement. Thymocyte development in zap-70-/- mice is blocked at the CD4+CD8+ TCR(lo) stage. The presence of Syk in the thymus has raised the possibility that Syk may be able to mediate TCR function. To determine if Syk can play a role in thymocyte development, we generated zap-70-/- mice expressing a human syk cDNA. Syk expression restored both thymocyte development and function. In addition, Syk function required the CD45 transmembrane protein tyrosine phosphatase. Hence, ZAP-70 and Syk can play overlapping functions and exhibit similar regulatory mechanisms in mediating alphabeta T cell development.

Publication types

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

MeSH terms

  • Animals
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • Enzyme Precursors / biosynthesis
  • Enzyme Precursors / genetics
  • Enzyme Precursors / physiology*
  • Epithelium / growth & development
  • Epithelium / ultrastructure
  • Female
  • Gene Expression
  • Humans
  • Intestines / growth & development
  • Intestines / ultrastructure
  • Intracellular Signaling Peptides and Proteins
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / physiology
  • Mice
  • Mice, Inbred C57BL
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology*
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis
  • Receptors, Antigen, T-Cell, gamma-delta / physiology
  • Signal Transduction / physiology
  • Syk Kinase
  • T-Lymphocytes / cytology
  • T-Lymphocytes / physiology*
  • T-Lymphocytes / ultrastructure
  • Thymus Gland / cytology
  • Thymus Gland / growth & development*
  • Thymus Gland / ultrastructure
  • Transgenes
  • ZAP-70 Protein-Tyrosine Kinase

Substances

  • DNA, Complementary
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • Zap70 protein, mouse
  • Leukocyte Common Antigens