The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 protein in T cell receptor signaling

Thomas Trüb, J. Daniel Frantz, Masaya Miyazaki, Hamid Band, Steven E. Shoelson

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

We have characterized an SH3-SH2-SH3 linker protein that is prominently expressed in lymphoid tissues. This protein has 58% sequence identity to Grb2. An identical protein called Grap has been found in hematopoietic cells. In Jurkat cells, T cell receptor activation leads to the association of Grap with phosphoproteins p36/38 and, to a lesser degree, Shc. This interaction is mediated by the Grap SH2 domain, which has similar binding specificity to the Grb2 SH2 domain. Grap also associates via its SH3 domains with Sos, the Ras guanine nucleotide exchange factor; with dynamin, a GTPase involved in membrane protein trafficking; and with Sam68, a nuclear RNA-binding protein that serves as a substrate of Src kinases during mitosis. T cell activation effects an increase in Grap association with p36/38, Shc, Sos, and dynamin. Sam68 binding is constitutive. Phospholipase C-γ1 and Fyn are also found in activated Grap signaling complexes, although these interactions may not be direct. We conclude that Grap is a prominent component of lymphocyte receptor signaling. Based on the known functions of bound effector molecules, Grap- mediated responses to antigen challenge may include endocytosis of the T cell receptor, cellular proliferation, and regulated entry into the cell cycle.

Original languageEnglish (US)
Pages (from-to)894-902
Number of pages9
JournalJournal of Biological Chemistry
Volume272
Issue number2
DOIs
StatePublished - Jan 25 1997
Externally publishedYes

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src Homology Domains
T-Cell Antigen Receptor
Dynamins
ras Guanine Nucleotide Exchange Factors
Chemical activation
Association reactions
Nuclear RNA
Proteins
Jurkat Cells
RNA-Binding Proteins
T-cells
Lymphocytes
src-Family Kinases
GTP Phosphohydrolases
Phosphoproteins
Type C Phospholipases
Lymphoid Tissue
Protein Transport
Nuclear Proteins
Endocytosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 protein in T cell receptor signaling. / Trüb, Thomas; Frantz, J. Daniel; Miyazaki, Masaya; Band, Hamid; Shoelson, Steven E.

In: Journal of Biological Chemistry, Vol. 272, No. 2, 25.01.1997, p. 894-902.

Research output: Contribution to journalArticle

Trüb, Thomas ; Frantz, J. Daniel ; Miyazaki, Masaya ; Band, Hamid ; Shoelson, Steven E. / The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 protein in T cell receptor signaling. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 2. pp. 894-902.
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