Maintenance has been completed and SciCrunch services have been restored. We apologize for any inconvenience it may have caused.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein.

Using the yeast two-hybrid system, we screened for proteins interacting with presenilin 2 (PS2) and cloned DRAL. DRAL is an LIM-only protein containing four LIM domains and an N-terminal half LIM domain. Previously DRAL has been cloned as a co-activator of the androgen receptor and as a protein interacting with a DNA replication regulatory protein, hCDC47. Our yeast two-hybrid assay showed that DRAL interacted with a hydrophilic loop region (amino acids 269-298) in the endoproteolytic N-terminal fragment of PS2, but not that of PS1, although the region 269-298 of PS2 and the corresponding PS1 sequence differ by only three amino acids. Each point mutation within this region, R275A, T280A, Q282A, R284A, N285A, P287T, I288L, F289A and S296A, in PS2 abolished the binding. This suggests that DRAL recognizes the PS2 structure specifically. The in vitro interaction was confirmed by affinity column assay and the physiological interactions between endogenous PS2 and DRAL by co-immunoprecipitation from human lung fibroblast MRC5 cells. Furthermore, in PS2-overexpressing HEK293 cells, we found an increase in the amount of DRAL in the membrane fraction and an increase in the amount of DRAL that was co-immunoprecipitated with PS2. The potential role of DRAL in the cellular signaling suggests that DRAL functions as an adaptor protein that links PS2 to an intracellular signaling.

Pubmed ID: 11001931


  • Tanahashi H
  • Tabira T


Human molecular genetics

Publication Data

September 22, 2000

Associated Grants


Mesh Terms

  • Alzheimer Disease
  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Chromatography, Affinity
  • Homeodomain Proteins
  • Humans
  • LIM-Homeodomain Proteins
  • Membrane Proteins
  • Molecular Sequence Data
  • Muscle Proteins
  • Mutation
  • Organ Specificity
  • Precipitin Tests
  • Presenilin-1
  • Presenilin-2
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger
  • Rats
  • Signal Transduction
  • Transcription Factors
  • Two-Hybrid System Techniques