MEK partner 1 (MP1): Regulation of oligomerization in MAP kinase signaling

Specificity in signal transduction can be achieved through scaffolds, anchors, and adapters that assemble generic signal transduction components in specific combinations and locations. MEK Partner‐1 (MP1) was identified as a potential “scaffold” protein for the mammalian extracellular signal‐regulat...

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Published in:Journal of cellular biochemistry 2005-03, Vol.94 (4), p.708-719
Main Authors: Sharma, Charu, Vomastek, Tomáš, Tarcsafalvi, Adel, Catling, Andrew D., Schaeffer, Hans-Joerg, Eblen, Scott T., Weber, Michael J.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Cell Line
Cricetinae
Enzyme Activation
ERK1
Gene Deletion
Humans
MAP kinase
MAP Kinase Signaling System
MEK1
Mitogen-Activated Protein Kinase 3 - metabolism
MP1
Mutation - genetics
Phosphorylation
Protein Binding
ras Proteins - genetics
ras Proteins - metabolism
scaffold
Serum
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Summary:Specificity in signal transduction can be achieved through scaffolds, anchors, and adapters that assemble generic signal transduction components in specific combinations and locations. MEK Partner‐1 (MP1) was identified as a potential “scaffold” protein for the mammalian extracellular signal‐regulated kinase (ERK) pathway. To gain insight into the interactions of MP1 with the ERK pathway, we analyzed the ability of MP1 to bind to MEK1, ERK1, and to itself, and the regulation of these interactions. Gel filtration of cell lysates revealed two major MP1 peaks: a broad high molecular weight peak and a 28 kDa complex. An MP1 mutant that lost MEK1 binding no longer enhanced RasV12‐stimulated ERK1 activity, and functioned as a dominant negative, consistent with the concept that MP1 function depends on facilitating these oligomerizations. Activation of the ERK pathway by serum or by RasV12 did not detectably affect MP1–MP1 dimerization or MP1–MEK1 interactions, but caused the dissociation of the MP1‐ERK1 complex. Surprisingly, pharmacological inhibition of ERK activation did not restore the complex, suggesting that regulation of complex formation occurs independently of ERK phosphorylation. These results support the concept that MP1 functions as a regulator of MAP kinase signaling by binding to MEK1 and regulating its association with a larger signaling complex that may sequentially service multiple molecules of ERK. © 2004 Wiley‐Liss, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.20344