X

Forgot your Password

If you have forgotten your password, please enter your account email below and we will reset your password and email you the new password.

X

Login to SciCrunch

X

Register an Account

Delete Saved Search

Are you sure you want to delete this saved search?

NO

NIF LinkOut Portal

FILTERS

Gas6 anti-apoptotic signaling requires NF-kappa B activation.

Authors:
Demarchi F, Verardo R, Varnum B, Brancolini C, Schneider C
Affiliation:
Journal:
The Journal of biological chemistry

Abstract

The growth arrest-specific 6 gene product Gas6 is a growth and survival factor related to protein S. Gas6 is the ligand of Axl receptor tyrosine kinase; upon binding to its receptor Gas6 activates the phosphatidylinositol 3-OH kinase (PI3K) and its downstream targets S6K and Akt. Gas6 anti-apoptotic signaling was previously shown to require functional PI3K and Akt and to involve Bad phosphorylation in serum-starved NIH 3T3 cells. Here we demonstrate that Gas6 induces a rapid and transient increase in nuclear NF-kappa B binding activity coupled to transcription activation from NF-kappa B-responsive promoters and increase in Bcl-x(L) protein level. Gas6 survival function is impaired in cells lacking p65/RelA and in NIH 3T3 cells transfected with a dominant negative I kappa B, indicating that NF-kappa B activation plays a central role in promoting survival in this system. Moreover, NF-kappa B activation can be blocked by a dominant negative Akt and by wortmannin, an inhibitor of PI3K, thus suggesting that NF-kappa B activation is a downstream event with respect to PI3K and Akt, as already described for other growth factors. In addition, we show that glycogen synthase kinase 3, which is phosphorylated in response to Gas6, can physically associate with NFKB1/p105 in living cells and can phosphorylate it in vitro. Furthermore, Gas6 treatment is coupled to a decrease in p105 protein level. Altogether these data suggest the involvement of NF-kappa B and glycogen synthase kinase 3 in Gas6 anti-apoptotic signaling and unveil a possible link between these survival pathways.

  1. Welcome

    Welcome to NIF. Explore available research resources: data, tools and materials, from across the web

  2. Community Resources

    Search for resources specially selected for NIF community

  3. More Resources

    Search across hundreds of additional biomedical databases

  4. Literature

    Search Pub Med abstracts and full text from PubMed Central

  5. Insert your Query

    Enter your search terms here and hit return. Search results for the selected tab will be returned.

  6. Join the Community

    Click here to login or register and join this community.

  7. Categories

    Narrow your search by selecting a category. For additional help in searching, view our tutorials.

  8. Query Info

    Displays the total number of search results. Provides additional information on search terms, e.g., automated query expansions, and any included categories or facets. Expansions, filters and facets can be removed by clicking on the X. Clicking on the + restores them.

  9. Search Results

    Displays individual records and a brief description. Click on the icons below each record to explore additional display options.

X