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Epithelial morphogenesis
Epithelial
cells are capable of undergoing marked changes in cell motility and cell morphology
in response to growth factor activation. Cells derived from the kidney tubule
can form 3-dimensional tubular structures with central lumens when cultured in
the presence of specific compounds such as hepatocyte growth factor. Our laboratory
is interested in defining the signaling pathways that regulate these processes
and determining the effector proteins that mediate the actual morphologic changes.
We have identified the phosphoinositide 3-kinase and MAPK pathways as critical
regulators of epithelial cell migration and morphogenesis and have identified
a novel role for ERK at the cell membrane as a key activator of focal adhesion
complex turnover. Our present focus is to establish the molecular determinants
of ERK recruitment to the membrane and determine how ERK regulates focal adhesions.
The ultimate goal of our studies is to determine the factors that mediate repair
of the injured kidney tubule and define approaches to augment the process of repair.
In this regard, we have recently found that a major component of the repair process
involves the recruitment and differentiation of adult stem cells from the bone
marrow to the kidney. We are presently pursuing the mechanism of mobilization,
targeting, and differentiation of these cells using microarray and in vitro differentiation
assays. Recent publications: Liu
Z-X, Yu CF, Nickel CH, Thomas S, and Cantley LG. Hepatocyte growth factor (HGF)
induces
ERK-dependent paxillin phosphorylation and regulates paxillin/FAK association.
J.Biol.Chem., 2002; 277: 10452-1-458. Yu
C.F., Liu Z-X, and Cantley LG. ERK
negatively regulates the EGF-mediated interaction of Gab1 and the PI 3-kinase.
J.Biol.Chem., 2002; 277: 19382-19388.
Kale S, Karihaloo A, Clark P, Kashgarian M, Krause D, and Cantley LG.
Bone marrow stem cells contribute to repair of the is chemically injured renal
tubule. J.Clin.Inv.2003;
112,42-49 Ishibe
S., Joly D., Liu Z-X., and Cantley L.G.
Phosphorylation-dependent Paxillin-ERK association mediates Hepatocyte Growth
Factor-stimulated epithelial morphogenesis. Mol. Cell, 2003; 12, 1275-1285.
Lloyd.Cantley@yale.edu
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