title: Common docking domain mutation E322K of the ERK2 gene is infrequent in oral squamous cell carcinomas.
abstract: BACKGROUND
  Mutations in the MAPK (Mitogen Activated Protein Kinase) signaling pathway - EGFR/Ras/ RAF/MEK have been associated with the development of several carcinomas. ERK2, a downstream target of the MAPK pathway and a founding member of the MAPK family is activated by cellular signals emanating at the cell membrane. Activated ERK2 translocates into the nucleus to transactivate genes that promote cell proliferation. MKP - a dual specific phosphatase - interacts with activated ERK2 via the common docking (CD) domain of the later to inactivate (dephosphorylate) and effectively terminate further cell proliferation. A constitutively active form of ERK2 carrying a single point mutation (E322K) in its CD domain, was earlier reported by our laboratory. In the present study, we investigated the prevalence of this CD domain E322K mutation in 88 well differentiated OSCC tissue samples.
  
  
  METHODS
  Genomic DNA specimens isolated from 88 oral squamous cell carcinoma tissue samples were amplified with primers flanking the CD domain of the ERK2 gene. Subsequently, PCR amplicons were gel purified and subjected to direct sequencing to screen for mutations.
  
  
  RESULTS
  Direct sequencing of eighty eight OSCC samples identified an E322K CD domain mutation in only one (1.1%) OSCC sample.
  
  
  CONCLUSIONS
  Our result indicates that mutation in the CD domain of ERK2 is rare in OSCC patients, which suggests the role of genetic alterations in other mitogenic genes in the development of carcinoma in the rest of the patients. Nevertheless, the finding is clinically significant, as the relatively rare prevalence of the E322K mutation in OSCC suggests that ERK2, being a common end point signal in the multi-hierarchical mitogen activated signaling pathway may be explored as a viable drug target in the treatment of OSCC.
authors: Department of Periodontia, Sree Balaji Medical and Dental College and Hospital, Bharath University, Chennai, India. drarvindram@yahoo.co.in
authors: Gopalakrishnan Mohan
authors: GM
authors: Valiathan
authors: Siji Jacob
authors: SJ
authors: Thenumgal
authors: Bhaskar
authors: B
authors: Jayaraman
authors: Arunmozhi
authors: A
authors: Palaniyandi
authors: Hemalatha
authors: H
authors: Ramkumar
authors: Keerthivasan
authors: K
authors: Jayakumar
authors: Sajeev
authors: S
authors: Bhaskaran
authors: Arvind
authors: A
authors: Ramanathan
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics; D009154:Mutation; D010766:Phosphorylation
chemical_list: D019950:Mitogen-Activated Protein Kinase 1