Tpl-2 acts in concert with Ras and Raf-1 to activate mitogen-activated protein kinase - PubMed (original) (raw)

Tpl-2 acts in concert with Ras and Raf-1 to activate mitogen-activated protein kinase

C Patriotis et al. Proc Natl Acad Sci U S A. 1994.

Abstract

Mitogenic signals initiated at the plasma membrane by extracellular factors acting on receptor tyrosine kinases or G protein-coupled receptors are transmitted to the nucleus through an intricate signaling network. Components of this network participate, upon stimulation, in a complex array of phosphorylation-dependent protein-protein interactions which leads to the formation of transient multimolecular complexes. Complexes containing products of the protooncogenes ras and raf-1 and the protein kinase MEK-1 activate the mitogen-activated protein kinases (MAPKs), which play a central role in the integration of different mitogenic signals by directly phosphorylating cytoplasmic and nuclear targets. In this report we present evidence that the kinase encoded by the tumor progression locus 2 gene (Tpl-2) contributes to the activation of the MAPK cascade. MAPK activation induced by the Tpl-2 protein is blocked by dominant negative mutants of Ras and Raf-1, whereas a kinase-deficient Tpl-2 mutant down-regulates mitogenic signals induced by v-Ha-Ras or v-Raf. These data suggest that Tpl-2 activates the MAPK cascade, perhaps through its participation in the assembly of Ras/Raf-1-containing multimolecular complexes.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):215-29 - PubMed
    1. Nature. 1994 Jun 2;369(6479):411-4 - PubMed
    1. Cell Regul. 1991 Dec;2(12):965-78 - PubMed
    1. Mol Cell Biol. 1992 May;12(5):2222-9 - PubMed
    1. EMBO J. 1992 Jun;11(6):2159-66 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources