Ganglioside GM3 activates ERKs in human lymphocytic cells

Garofalo, Tina; Sorice, Maurizio; Misasi, Roberta; Cinque, B.; Vincenzo, Mattei; Pontieri, Giuseppe; Cifone, M. G.; Pavan, Antonio

In this study we analyzed the signaling pathway triggered by GM3 in lymphoblastoid T-cells. In these cells, GM3 induced cPLA(2) activation, arachidonic acid release, and PKC-delta translocation. In order to clarify the upstream molecular signals triggered by GM3, we analyzed the activation of extracellular signal-regulated kinase (ERK)s, a downstream effector of Ras-regulated cytoplasmic kinase cascade. Our results showed that GM3 treatment led to rapid ERK phosphorylation in lymphoblastoid T-cells, as detected by anti-phospho-p44/42 MAP kinase. Similar findings were found in human peripheral blood lymphocytes. Moreover, we showed that GM3 specifically phosphorylated ERK-2, as revealed by anti-phosphotyrosine reactivity on both cell free lysates and ERKs immunoprecipitates. The role of the CD4 cytoplasmic domain in GM3-triggered signaling pathway was investigated using A2.01/CD4-cyt399 cells, which had been transfected with a mutant form of CD4 lacking the bulk of the cytoplasmic domain. In these cells GM3 induced cPLA(2) activation, arachidonic acid release, and PKC-delta translocation, but not CD4 endocytosis, indicating that the CD4 cytoplasmic domain plays a key role in GM3-triggered CD4 endocytosis and the GM3-triggered biochemical pathway is upstream of CD4 phosphorylation. These findings strongly suggest that GM3 triggers a novel signaling pathway involved in the regulation of cellular functions.

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Titolo:	Ganglioside GM3 activates ERKs in human lymphocytic cells
Autori:	GAROFALO, TINA SORICE, Maurizio MISASI, Roberta B. Cinque Vincenzo Mattei PONTIERI, Giuseppe M. G. Cifone PAVAN, Antonio mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2002
Rivista:	JOURNAL OF LIPID RESEARCH
Handle:	http://hdl.handle.net/11573/250356
Appartiene alla tipologia:	01a Articolo in rivista

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