Activation of the apoptotic JNK pathway through the Rac1-binding scaffold protein POSH.
The JNKs (c-Jun N-terminal protein kinases) play important roles in a variety of physiological and pathological functions including induction of apoptosis. A major pathway by which JNKs are activated in response to apoptotic stimuli includes the GTP*Rac1-binding scaffold protein POSH (plenty of SH3s). POSH acts as a scaffold for binding and autoactivation of the MLK family of MKKK proteins, which in turn phosphorylate and activate the MKK family members MKK4 and 7, which in turn phosphorylate JNKs. In this chapter, we describe methods and techniques that have been successfully used to study the POSH-dependent apoptotic JNK pathway. Use of these techniques may lead to a better understanding of the components of this pathway and of how it is suppressed in viable cells and rapidly activated in response to apoptotic stimuli.
Xu
Zhiheng
Z
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Greene
Lloyd A
LA
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
C498193:SH3RF1 protein, human; D044767:Ubiquitin-Protein Ligases; D048031:JNK Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein