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Vol. 11, Issue 10, 3299-3313, October 2000
and
*Departments of Medicine and Cell Biology, Washington University,
St. Louis, Missouri 63110; and Cellular adhesive events affect cell proliferation and
differentiation decisions. How cell surface events mediating adhesion transduce signals to the nucleus is not well understood. After cell-cell or cell-substratum contact, cytosolic proteins are
recruited to clustered adhesion receptor complexes. One such family of
cytosolic proteins found at sites of cell adhesion is the Zyxin family
of LIM proteins. Here we demonstrate that the family member Ajuba was
recruited to the cell surface of embryonal cells, upon aggregate formation, at sites of cell-cell contact. Ajuba contained a functional nuclear export signal and shuttled into the nucleus. Importantly, accumulation of the LIM domains of Ajuba in the nucleus of P19 embryonal cells resulted in growth inhibition and spontaneous endodermal differentiation. The differentiating effect of Ajuba mapped
to the third LIM domain, whereas regulation of proliferation mapped to
the first and second LIM domains. Ajuba-induced endodermal differentiation of these cells correlated with the capacity to activate
c-Jun kinase and required c-Jun kinase activation. These results
suggest that the cytosolic LIM protein Ajuba may provide a new
mechanism to transduce signals from sites of cell adhesion to the
nucleus, regulating cell growth and differentiation decisions during
early development.
Physiology Department,
University College London, London WC1E 6BT, England
Corresponding author. E-mail address:
longmorg{at}medicine.wustl.edu.
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