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Volume 272, Number 49, Issue of December 5, 1997 pp. 30806-30811
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Cbl-mediated Regulation of T Cell Receptor-induced AP1 Activation
IMPLICATIONS FOR ACTIVATION VIA THE Ras SIGNALING PATHWAY

(Received for publication, June 23, 1997, and in revised form, August 25, 1997)

From the Laboratory of Immunobiology, Division of Monoclonal Antibodies, Office of Therapeutics Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

The functional role of Cbl in regulating T cell receptor (TCR)-mediated signal transduction pathways is unknown. This study uses Cbl overexpression in conjunction with a Ras-sensitive AP1 reporter construct to examine its role in regulating TCR-mediated activation of the Ras pathway. Cbl overexpression in Jurkat T cells inhibited AP1 activity after TCR ligation. However, AP1 induction by 4-phorbol 12-myristate 13-acetate, which up-regulates Ras activity in a protein kinase C-dependent, TCR/tyrosine kinase-independent manner, was not affected by Cbl overexpression. Cbl overexpression also did not affect AP1 induction by an activated Ras protein or a membrane-bound form of the guanine nucleotide exchange factor Sos. In addition, activation of the mitogen-activated protein kinase Erk2 was decreased by Cbl overexpression. Therefore, Cbl regulates events that are required for full TCR-mediated Ras activation, and data are presented to support a model whereby Cbl regulates events required for Ras activation via its association with Grb2.

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