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Differential Activation of Stress-Activated Protein Kinase Kinases SKK4/MKK7 and SKK1/MKK4 by the Mixed-Lineage kinase-2 and Mitogen-Activated Protein Kinase Kinase (MKK) kinase-1

Differential Activation of Stress-Activated Protein Kinase Kinases SKK4/MKK7 and SKK1/MKK4 by the Mixed-Lineage kinase-2 and Mitogen-Activated Protein Kinase Kinase (MKK) kinase-1

A Cuenda, D S Dorow

Biochem J. 1998 Jul 1;333 ( Pt 1)(Pt 1):11-5.

PMID: 9639556

Abstract:

Overexpression of the protein kinases mixed-lineage kinase-2 (MLK2) or mitogen-activated protein kinase (MAPK) kinase kinase-1 (MEKK1) is known to trigger the activation of stress-activated protein kinase (SAPK1)/c-Jun N-terminal kinase (JNK). Here we demonstrate that MLK2 activates SAPK kinase-1 (SKK1)/MAPK kinase 4 (MKK4) and SKK4/MKK7, the two known direct activators of SAPK1/JNK (both in transfection studies and in vitro). In contrast, MEKK1 activates SKK1/MKK4 more efficiently than MLK2, but barely activates SKK4/MKK7. Since SKK4/MKK7 (but not SKK1/MKK4) is activated by interleukin-1 and tumour necrosis factor in several cells and tissues, we suggest that MEKK1 does not mediate the activation of SKK4/MKK7 and SAPK1/JNK induced by these pro-inflammatory cytokines. MLK2 and MEKK1 also activated SKK2/MKK3 and SKK3/MKK6, the direct upstream activators of SAPK2a/p38.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42411893	MKK6/SKK3, active human			Price

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