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Immunity. 1998 Jan;8(1):31-41.

Cooperation between Syk and Rac1 leads to synergistic JNK activation in T lymphocytes.

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Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636, USA.


The MAP kinase (MAPK) JNK but not ERK is synergistically activated during costimulation of T cells. We examined how protein tyrosine kinases (PTKs) and GTPases differentially regulate JNK and ERK in T cells. While PTKs are not selective, small GTPases display distinct MAPK-activating functions. Whereas Ras activates ERK, Rac activates JNK. Rac cooperates with a Syk-generated signal to enhance JNK activation and appears to be at a nodal point for pathways emanating from CD28, calcineurin, and protein kinase C. AP-1- and NF-AT-dependent reporters are stimulated by Rac and Syk and are dependent on JNK. Unlike Syk, the PTK Lck activates JNK but does not cooperate with Rac, resulting in weak AP-1 and NF-AT activation. Therefore, signals generated by PTKs are functionally distinct and need to be integrated to induce transcriptional responses.

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