Differential effects of Cbl and 70Z/3 Cbl on T cell receptor-induced phospholipase Cgamma-1 activity.
We demonstrate that the differential effects Cbl and oncogenic 70Z/3 Cbl have on Ca(2+)/Ras-sensitive NF-AT reporters is partially due to their opposing ability to regulate phospholipase Cgamma1 (PLCgamma1) activation as demonstrated by analysis of the activation of an NF-AT reporter construct and PLCgamma1-mediated inositol phospholipid (PI) hydrolysis. Cbl over-expression resulted in reduced T cell receptor-induced PI hydrolysis, in the absence of any effect on PLCgamma1 tyrosine phosphorylation. In contrast, expression of 70Z/3 Cbl led to an increase in basal and OKT3-induced PLCgamma1 phosphorylation and PI hydrolysis. These data indicate that Cbl and 70Z/3 Cbl differentially regulate PLCgamma1 phosphorylation and activation. The implications of these data on the mechanism of Cbl-mediated signaling regulation are discussed.
Graham
L J
LJ
Laboratory of Immunobiology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, HFM-564, Building 29B, Room 3NN10, 29 Lincoln Drive MSC 4555, Bethesda, MD 20892-4555, USA.
DeBell
K E
KE
Verí
M
M
Stoica
B
B
Mostowski
H
H
Bonvini
E
E
Rellahan
B
B
D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D016853:Muromonab-CD3 / Q000494:pharmacology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D050722:Oncogene Protein v-cbl; D010716:Phosphatidylinositols / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D010738:Type C Phospholipases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016853:Muromonab-CD3; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D050722:Oncogene Protein v-cbl; D010716:Phosphatidylinositols; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D019000:Phosphotyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D019703:Calcineurin; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D018631:ras Proteins; C067419:CBL protein, human; D013755:Tetradecanoylphorbol Acetate