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.