Abstract
Signaling by the T-cell antigen receptor (TCR) involves both phospholipase C (PLC)-gamma 1 and p21ras activation. While failing to induce Shc/Grb2 association, ligation of the TCR/CD3 receptor in Jurkat T-cells induced hSos1-Grb2 complexes. In addition to hSos1, Grb2 participates in the formation of a tyrosine phosphoprotein complex that includes 145-, 95-, 70-, 54-, and 36-38-kDa proteins. p145 was identified as PLC-gamma 1 and p70 as the protein tyrosine kinase, ZAP-70. Although of the same molecular weight, p95 was not recognized by an anti-serum to p95 Vav. The SH2 domains of Grb2 and PLC-gamma 1 were required for the formation of this protein complex. In anti-CD3-treated cells, Grb2 redistributed from the cytosol to a particulate cell compartment along with p36/p38, ZAP-70, and PLC-gamma 1. Part of the Grb2 complex associated with the particulate compartment could be extracted with Nonidet P-40, while the rest was Nonidet P-40 insoluble. In both the detergent-soluble and -insoluble fractions, Grb2 coimmunoprecipitated with the zeta-chain of the TCR. Taken together, these results indicate that anti-CD3 induces Grb2-hSos1-PLC-gamma 1-p36/p38-ZAP70 complexes, which localize in the vicinity of TCR-zeta.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Cell Compartmentation
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GRB2 Adaptor Protein
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Guanine Nucleotide Exchange Factors
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Humans
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Isoenzymes / metabolism
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Ligands
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Macromolecular Substances
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Octoxynol
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Phospholipase C gamma
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Phosphoproteins / metabolism*
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Polyethylene Glycols
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Protein Binding
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism*
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Receptors, Antigen, T-Cell / metabolism*
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Shc Signaling Adaptor Proteins
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Signal Transduction / physiology*
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Solubility
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Structure-Activity Relationship
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T-Lymphocytes / metabolism*
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Type C Phospholipases / metabolism
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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GRB2 Adaptor Protein
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GRB2 protein, human
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Guanine Nucleotide Exchange Factors
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Isoenzymes
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Ligands
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Macromolecular Substances
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Phosphoproteins
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Proteins
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Receptors, Antigen, T-Cell
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SHC1 protein, human
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Shc Signaling Adaptor Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Polyethylene Glycols
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Octoxynol
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Nonidet P-40
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human
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Type C Phospholipases
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Phospholipase C gamma