Activation of extracellular signal‐regulated protein kinase (ERK/MAP kinase) following CD28 cross‐linking: activation in cells lacking p56lck

A. August, B. Dupont

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Abstract: T lymphocytes require two signals for activation. Recognition of antigen/MHC complexes by the T cell receptor delivers the first signal, while a second signal, delivered by the cell surface receptors CD80 and/or CD86 binding to the T cell surface molecule CD28, has been shown to be effective for the initiation of effective T cell responses. While some of the cytoplasmic effector molecules involved in T cell receptor signaling is known, little is known regarding those involved in the co‐stimulation of T cells by CD28. Using the T cell leukemic cell line Jurkat as a model for T cell activation, we demonstrate that cross‐linking CD28 using monoclonal antibodies causes tyrosine phosphorylation and activation of MAP kinase/ERK. This activation was rapid, peaking at approximately 5 minutes post CD28 cross‐linking, and transient. Activation of MAP kinase/ERK occurred 3 fold less efficiently in a Jurkat line lacking functional p56lck (JCAM.1), and was almost undetectable in a line lacking CD45 (J45.01). These results suggest that CD28 cross‐linking can activate intracellular signaling pathways via several different tyrosine kinases. Thus CD28 signaling can activate src family kinases lck and fyn, as well as the Tec family kinase emt/ick. Activation of any one or a combination of these tyrosine kinases may be sufficient for the activation of MAPK following CD28 cross‐linking. Activation of MAPK has been shown to cause activation of AP‐I and other transcription factors via serine and/or threonine phosphorylation. This observation thus connects signaling via CD28 to activation of nuclear transcription factors required for the transcription of T cell genes including lymphokines such as IL‐2 and GM‐CSF.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalTissue Antigens
Volume46
Issue number3
DOIs
StatePublished - Sep 1995

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Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Crosslinking
Protein Kinases
T-cells
Chemical activation
T-Lymphocytes
T-Cell Antigen Receptor
Protein-Tyrosine Kinases
Phosphorylation
Phosphotransferases
Transcription Factors
src-Family Kinases
Lymphokines
Cell Surface Receptors
Threonine
Serine
Interleukin-2
Tyrosine
Molecules

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

Cite this

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abstract = "Abstract: T lymphocytes require two signals for activation. Recognition of antigen/MHC complexes by the T cell receptor delivers the first signal, while a second signal, delivered by the cell surface receptors CD80 and/or CD86 binding to the T cell surface molecule CD28, has been shown to be effective for the initiation of effective T cell responses. While some of the cytoplasmic effector molecules involved in T cell receptor signaling is known, little is known regarding those involved in the co‐stimulation of T cells by CD28. Using the T cell leukemic cell line Jurkat as a model for T cell activation, we demonstrate that cross‐linking CD28 using monoclonal antibodies causes tyrosine phosphorylation and activation of MAP kinase/ERK. This activation was rapid, peaking at approximately 5 minutes post CD28 cross‐linking, and transient. Activation of MAP kinase/ERK occurred 3 fold less efficiently in a Jurkat line lacking functional p56lck (JCAM.1), and was almost undetectable in a line lacking CD45 (J45.01). These results suggest that CD28 cross‐linking can activate intracellular signaling pathways via several different tyrosine kinases. Thus CD28 signaling can activate src family kinases lck and fyn, as well as the Tec family kinase emt/ick. Activation of any one or a combination of these tyrosine kinases may be sufficient for the activation of MAPK following CD28 cross‐linking. Activation of MAPK has been shown to cause activation of AP‐I and other transcription factors via serine and/or threonine phosphorylation. This observation thus connects signaling via CD28 to activation of nuclear transcription factors required for the transcription of T cell genes including lymphokines such as IL‐2 and GM‐CSF.",
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Activation of extracellular signal‐regulated protein kinase (ERK/MAP kinase) following CD28 cross‐linking : activation in cells lacking p56lck. / August, A.; Dupont, B.

In: Tissue Antigens, Vol. 46, No. 3, 09.1995, p. 155-162.

Research output: Contribution to journalArticle

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