Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in MEKs that are regulated by Raf family enzymes but is missing from MEKs and SEKs activated independently of Raf, we sought to investigate the role of this sequence in MEK1 and MEK2 regulation and function. Deletion of the PR sequence from MEK1 blocked the ability of MEK1 to associate with members of the Raf family and markedly attenuated activation of the protein in vivo following growth factor stimulation. In addition, this sequence was necessary for efficient activation of MEK1 in vitro by B-Raf but dispensable for activation by a novel MEK1 activator which we have previously detected in fractionated fibroblast extracts. Furthermore, we found that a phosphorylation site within the PR sequence of MEK1 was required for sustained MEK1 activity in response to serum stimulation of quiescent fibroblasts. Consistent with this observation, we observed that MEK2, which lacks a phosphorylation site at the corresponding position, was activated only transiently following serum stimulation. Finally, we found that deletion of the PR sequence from a constitutively activated MEK1 mutant rendered the protein nontransforming in Rat1 fibroblasts. These observations indicate a critical role for the PR sequence in directing specific protein-protein interactions important for the activation, inactivation, and downstream functioning of the MEKs.

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An experiment was conducted to determine if baby pigs develop intestinal hypersensitivity to dietary soy protein. Challenging nursery pigs with soybean meal following oral infusion of soybean meal from day 7 to day 14 of age resulted in villus atrophy and lower average daily gain by 28 days of age. At 56 days of age, there were no differences in weight gains between pigs fed soy protein and pigs fed milk protein. Pigs exposed to soybean meal before weaning had increased anti-soybean protein immnoglobulin titers at 4 wk (7.2 vs 4.0) and at 8 wk (7.6 vs 4.2). Thus, challenging baby pigs with soybean meal followed by feeding soybean meal resulted in an immune response as indicated by transient hypersensitivity at 4 wk and increased anti-soy protein titers. Also, growth was temporarily decreased at 4 weeks, but increased at 8 weeks.

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