title: Frequency decoding of calcium oscillations.
abstract: BACKGROUND
  Calcium (Ca(2+)) oscillations are ubiquitous signals present in all cells that provide efficient means to transmit intracellular biological information. Either spontaneously or upon receptor ligand binding, the otherwise stable cytosolic Ca(2+) concentration starts to oscillate. The resulting specific oscillatory pattern is interpreted by intracellular downstream effectors that subsequently activate different cellular processes. This signal transduction can occur through frequency modulation (FM) or amplitude modulation (AM), much similar to a radio signal. The decoding of the oscillatory signal is typically performed by enzymes with multiple Ca(2+) binding residues that diversely can regulate its total phosphorylation, thereby activating cellular program. To date, NFAT, NF-κB, CaMKII, MAPK and calpain have been reported to have frequency decoding properties.
  
  
  METHODS
  The basic principles and recent discoveries reporting frequency decoding of FM Ca(2+) oscillations are reviewed here.
  
  
  CONCLUSIONS
  A limited number of cellular frequency decoding molecules of Ca(2+) oscillations have yet been reported. Interestingly, their responsiveness to Ca(2+) oscillatory frequencies shows little overlap, suggesting their specific roles in cells.
  
  
  CONCLUSIONS
  Frequency modulation of Ca(2+) oscillations provides an efficient means to differentiate biological responses in the cell, both in health and in disease. Thus, it is crucial to identify and characterize all cellular frequency decoding molecules to understand how cells control important cell programs.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Smedler
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: per.uhlen@ki.se.
authors.forename: Per
authors.initials: P
authors.lastname: Uhlén
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000502:physiology; D050778:NFATC Transcription Factors / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D050778:NFATC Transcription Factors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: Calcium signaling; Frequency decoding; Frequency modulation