Abstract:
:Raf-1 is a serine-threonine protein kinase that functions as a central component of the mitogen-activated protein kinase signal transduction pathway. Raf-1 activity is currently assayed in vitro by either measuring 32P incorporation into MEK, Raf-1's only characterized substrate, or by using the phosphorylated MEK to initiate a coupled assay culminating in the phosphorylation of myelin basic protein by MAP kinase. These assays are plagued by a potential lack of specificity in the case of the former, and the time consuming and error-prone nature of the later indirect assay. In this report, we demonstrate a novel single step assay for Raf-1 kinase activity based on phosphorylation of recombinant MEK-1, detected using an activation-specific MEK antibody that recognizes MEK only when specifically phosphorylated by Raf-1 on Ser 217 and Ser 221. The assay readily detected stem cell factor-mediated Raf-1 activation. MEK phosphorylation by immunoprecipitated Raf-1 plateaued at 10 min following initiation of the kinase reaction and was completely dependent on the inclusion of Raf-1. There was a linear correlation between the degree of MEK phosphorylation and the amount of Raf-1 protein immunoprecipitated. In addition to detecting growth factor-mediated activation, the assay was also able to detect paclitaxel-mediated Raf-1 activation. This assay is rapid, sensitive, and specific and therefore is a marked improvement over currently utilized techniques.
journal_name
Oncogenejournal_title
Oncogeneauthors
Bondzi C,Grant S,Krystal GWdoi
10.1038/sj.onc.1203862subject
Has Abstractpub_date
2000-10-12 00:00:00pages
5030-3issue
43eissn
0950-9232issn
1476-5594journal_volume
19pub_type
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