PKC Phosphorylation Increases the Ability of AFAP-110 to Cross-Link Action Filaments

Details

• Personal Author:
  Baisden JM ; Cherezova L ; Flynn DC ; Guappone-Koay A ; Lee MY ; Mast T ; Mazloum N ; Pustula J ; Qian Y ; Shi X ; Summy JM ; Zot HG
• Description:
  The actin filament-associated protein and Src-binding partner, AFAP-110, is an adaptor protein that links signaling molecules to actin filaments. AFAP-110 binds actin filaments directly and multimerizes through a leucine zipper motif. Cellular signals downstream of Src(527F) can regulate multimerization. Here, we determined recombinant AFAP-110 (rAFAP-110)-bound actin filaments cooperatively, through a lateral association. We demonstrate rAFAP-110 has the capability to cross-link actin filaments, and this ability is dependent on the integrity of the carboxy terminal actin binding domain. Deletion of the leucine zipper motif or PKC phosphorylation affected AFAP-110's conformation, which correlated with changes in multimerization and increased the capability of rAFAP-110 to cross-link actin filaments. AFAP-110 is both a substrate and binding partner of PKC. On PKC activation, stress filament organization is lost, motility structures form, and AFAP-110 colocalizes strongly with motility structures. Expression of a deletion mutant of AFAP-110 that is unable to bind PKC blocked the effect of PMA on actin filaments. We hypothesize that upon PKC activation, AFAP-110 can be cooperatively recruited to newly forming actin filaments, like those that exist in cell motility structures, and that PKC phosphorylation effects a conformational change that may enable AFAP-110 to promote actin filament cross-linking at the cell membrane. [Description provided by NIOSH]
• Subjects:
  Genetics Occupational Health Safety
• Keywords:
  Cellular-reactions Cellular-structures Genes In-vitro-study Proteins
• ISSN:
  1059-1524
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; New York ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  13
• Issue:
  7
• NIOSHTIC Number:
  nn:20022978
• Citation:
  Mol Biol Cell 2002 Jul; 13(7):2311-2322
• Contact Point Address:
  Daniel C. Flynn, The Mary Babb Randolph Cancer Center and the Department of Microbiology and Immunology, West Virginia University, Morgantown, WV 26506-9300
• Email:
  dflynn@hsc.wvu.edu
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Disease and Injury: Hearing Loss
• Peer Reviewed:
  True
• Source Full Name:
  Molecular Biology of the Cell
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2f983d16f2635061f92d75b858c706b45310b178a8ed7197c2212b90eb0baacc19d166b3ded4dcb633edf418ce2ab88510eb3a42649dad2304ad9c994d9e4c9b
• Download URL:
  https://stacks.cdc.gov/view/cdc/199578/cdc_199578_DS1.pdf
• File Type:
  [PDF - 732.31 KB ]