Related Experiment Video

Updated: Aug 18, 2026

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
07:48

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist

Published on: April 25, 2018

Regulation of cytotoxic T lymphocyte-associated molecule-4 by Src kinases

E Chuang1, K M Lee, M D Robbins

  • 1Gwen Knapp Center for Lupus and Immunology Research, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|February 11, 1999
PubMed

Insights

Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is phosphorylated by Src kinases Fyn and Lck, influencing T cell signaling. This phosphorylation regulates CTLA-4

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) inhibits T cell responses.
  • The kinases responsible for CTLA-4 phosphorylation were previously unknown.
  • Tyrosine phosphorylation of CTLA-4 may regulate its interactions and signaling.

Purpose of the Study:

  • To identify the kinases that phosphorylate CTLA-4.
  • To investigate the functional consequences of CTLA-4 phosphorylation.
  • To elucidate the distinct signaling pathways activated by CTLA-4 and CD28 phosphorylation.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Transfection of kinases (Fyn, Lck, ZAP70) into cells expressing CTLA-4.
  • Analysis of CTLA-4 tyrosine phosphorylation in Jurkat T cells.
  • Investigation of protein-protein interactions using tyrosine phosphatase SHP-2 and phosphatidylinositol 3-kinase.

Main Results:

  • CTLA-4 associates with Src kinases Fyn and Lck.
  • Fyn and Lck induce tyrosine phosphorylation of CTLA-4 at Y201 and Y218.
  • Phosphorylation of CTLA-4 Y201 correlates with cell surface accumulation.
  • CTLA-4 phosphorylation leads to association with SHP-2, not PI3K.
  • Lck-induced CD28 phosphorylation recruits PI3K, not SHP-2.

Conclusions:

  • Src kinases Fyn and Lck phosphorylate CTLA-4, identifying them as key regulators.
  • CTLA-4 phosphorylation by Lck activates distinct pathways compared to CD28 phosphorylation.
  • The CTLA-4/Src kinase/SHP-2 complex has the potential to regulate T cell activation.

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...