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Related Experiment Videos

RIP2 is a Raf1-activated mitogen-activated protein kinase kinase.

T A Navas1, D T Baldwin, T A Stewart

  • 1Department of Endocrine Research, Genentech, Inc., South San Francisco, California 94080, USA.

The Journal of Biological Chemistry
|November 24, 1999
PubMed
Summary
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Receptor-interacting protein 2 (RIP2) kinase activates the extracellular signal-regulated kinase (ERK) pathway. This study reveals RIP2

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Signal Transduction

Background:

  • Receptor-interacting protein 2 (RIP2) is a serine-threonine kinase linked to the tumor necrosis factor (TNF) receptor complex.
  • RIP2 is involved in NF-kappaB activation and cell death, but the role of its kinase domain remains unclear.
  • The kinase domain of RIP2 is not essential for TNF-induced NF-kappaB activation or cell death.

Purpose of the Study:

  • To investigate the function of the RIP2 kinase domain.
  • To elucidate the role of RIP2 in activating signaling pathways beyond NF-kappaB.
  • To identify novel catalytic functions of RIP-like kinases in the TNF receptor superfamily.

Main Methods:

  • Investigated RIP2's role in activating the extracellular signal-regulated kinase (ERK) pathway.

Related Experiment Videos

  • Utilized in vivo and in vitro assays to demonstrate direct phosphorylation and activation of ERK2 by RIP2.
  • Examined the interaction of RIP2 with Ras-activated Raf1 and the effect of kinase-defective RIP2 variants on ERK2 activation.
  • Main Results:

    • RIP2 activates the ERK pathway, with its kinase activity being crucial for this process.
    • RIP2 phosphorylates and activates ERK2 both in vivo and in vitro.
    • RIP2-mediated ERK activation is dependent on its interaction with Raf1 and is triggered by TNFalpha but not epidermal growth factor.

    Conclusions:

    • This study identifies a novel pathway for ERK activation mediated by RIP2.
    • The findings ascribe the first catalytic function to a RIP-like kinase associated with the TNF receptor superfamily.
    • RIP2's kinase activity is essential for activating the ERK pathway, revealing a new role for this kinase.