Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Spatial Regulation of the cAMP-Dependent Protein Kinase during Chemotactic Cell Migration

Alan K. Howe, Linda C. Baldor, Brian P. Hogan and Susan S. Taylor
Proceedings of the National Academy of Sciences of the United States of America
Vol. 102, No. 40 (Oct. 4, 2005), pp. 14320-14325
Stable URL: http://www.jstor.org/stable/3376737
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Spatial Regulation of the cAMP-Dependent Protein Kinase during Chemotactic Cell Migration
Preview not available

Abstract

Historically, the cAMP-dependent protein kinase (PKA) has a paradoxical role in cell motility, having been shown to both facilitate and inhibit actin cytoskeletal dynamics and cell migration. In an effort to understand this dichotomy, we show here that PKA is regulated in subcellular space during cell migration. Immunofluorescence microscopy and biochemical enrichment of pseudopodia showed that type II regulatory subunits of PKA and PKA activity are enriched in protrusive cellular structures formed during chemotaxis. This enrichment correlates with increased phosphorylation of key cytoskeletal substrates for PKA, including the vasodilator-stimulated phosphoprotein (VASP) and the protein tyrosine phosphatase containing a PEST motif. Importantly, inhibition of PKA activity or its ability to interact with A kinase anchoring proteins inhibited the activity of the Rac GTPase within pseudopodia. This effect correlated with both decreased guanine nucleotide exchange factor activity and increased GTPase activating protein activity. Finally, inhibition of PKA anchoring, like inhibition of total PKA activity, inhibited pseudopod formation and chemotactic cell migration. These data demonstrate that spatial regulation of PKA via anchoring is an important facet of normal chemotactic cell movement.

Page Thumbnails

  • Thumbnail: Page 
[14320]
    [14320]
  • Thumbnail: Page 
14321
    14321
  • Thumbnail: Page 
14322
    14322
  • Thumbnail: Page 
14323
    14323
  • Thumbnail: Page 
14324
    14324
  • Thumbnail: Page 
14325
    14325