title: Identification of mitogen-activated protein kinase docking sites in enzymes that metabolize phosphatidylinositols and inositol phosphates.
abstract: BACKGROUND
  Reversible interactions between the components of cellular signaling pathways allow for the formation and dissociation of multimolecular complexes with spatial and temporal resolution and, thus, are an important means of integrating multiple signals into a coordinated cellular response. Several mechanisms that underlie these interactions have been identified, including the recognition of specific docking sites, termed a D-domain and FXFP motif, on proteins that bind mitogen-activated protein kinases (MAPKs). We recently found that phosphatidylinositol-specific phospholipase C-gamma1 (PLC-gamma1) directly binds to extracellular signal-regulated kinase 2 (ERK2), a MAPK, via a D-domain-dependent mechanism. In addition, we identified D-domain sequences in several other PLC isozymes. In the present studies we sought to determine whether MAPK docking sequences could be recognized in other enzymes that metabolize phosphatidylinositols (PIs), as well as in enzymes that metabolize inositol phosphates (IPs).
  
  
  RESULTS
  We found that several, but not all, of these enzymes contain identifiable D-domain sequences. Further, we found a high degree of conservation of these sequences and their location in human and mouse proteins; notable exceptions were PI 3-kinase C2-gamma, PI 4-kinase type IIbeta, and inositol polyphosphate 1-phosphatase.
  
  
  CONCLUSIONS
  The results indicate that there may be extensive crosstalk between MAPK signaling and signaling pathways that are regulated by cellular levels of PIs or IPs.
authors.affiliation: Department of Neurosciences University of New Mexico Health Sciences Center Albuquerque, NM 87131 USA. KCaldwell@salud.unm.edu.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Caldwell
authors.forename: Marcos
authors.initials: M
authors.lastname: Sosa
authors.forename: Colin T
authors.initials: CT
authors.lastname: Buckley