Kathleen J. Green, PhD Professor Pathology Molecular and cellular analysis of intercellular junction assembly and function Curricula: Cancer Biology Cell Biology E-mail:   kgreen@northwestern.edu

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Cell adhesion plays a crucial role in embryogenesis, differentiation of adult tissues and wound healing. Our laboratory is interested in the function and regulation of intercellular junction molecules in desmosomes and adherens junctions that mediate cell-cell adhesion and attachment of the cytoskeleton to the cell surface. The transmembrane proteins of these junctions, known as cadherins, have been demonstrated to suppress tumor growth and metastasis. Cadherin function may also be modulated by growth factors such as EGF and HGF during the acquisition of motility that accompanies wound healing and tumor cell invasion. Proteins that associate with the cytoplasmic domains of cadherins modulate their adhesive function but, surprisingly, can also be found in the nucleus. In some cases these so-called catenins have been shown play a critical role in intracellular signaling during development and in growth control via regulation of the APC (adenomatous polyposis coli) tumor suppressor protein.

Our lab employs a combination of cell biological (including living cell analyses using fluorescently tagged molecules), in vitro biochemical and transgenic mouse approaches to elucidate the function of cadherin complexes and their associated proteins in the junction and nucleus. The role of growth factor and oncogene-mediated tyrosine phosphorylation in modulating junction assembly and adhesion is also being addressed. Finally, desmosomal cadherins and their associated proteins are targets in both autoimmune and inherited epidermal blistering disorders, some of which can be fatal. We are using the yeast two hybrid interaction screen to identify possible new junction proteins that could be novel targets for mutation in human disease.

Publications:

Getsios, S., A.C. Huen, and K.J. Green (2004). Working out the strength and flexibility of desmosomes. Nature Reviews Cell Mol. Biol. 5: 271-281.

Chen, X, S. Kojima, G.G. Borisy and K.J. Green. (2003). p120 catenin associates with kinesin and facilitiates the transport of cadherin-catenin complexes to intercellular junctions. J. Cell Biol. 163: 547-557.

Huen AC, Park JK, Godsel LM, Chen X, Bannon LJ, Amargo EV, Hudson TY,Mongiu AK, Leigh IM, Kelsell DP, Gumbiner BM, Green KJ. Intermediate filament-membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength. J Cell Biol. 2002 Dec 23;159(6):1005-17.

Choi, H-J, S. Park-Snyder, L.T. Pascoe, K.J. Green and W.I. Weis. (2002). Structures of two fragments of the intermediate filament binding protein desmoplakin reveal a unique repeat motif structure. Nature Struct. Biol. 9 (8), pub online July 8, 2002.

Chen, X., S. Bonne, M. Hatzfeld, F. Van Roy, K.J. Green. (2002). Protein binding and functional characterization of plakophilin 2: evidence for its diverse roles in desmosomes and b-catenin signaling. J. Biol. Chem. 277: 10512-10522.

Gaudry, C.A., H.L. Palka, R.L. Dusek, A.C. Huen, M.J. Khandekar, L.G. Hudson, and K.J. Green. (2001). Tyrosine-phosphorylated plakoglobin is associated with desmogleins but not desmoplakin after epidermal growth factor receptor activation. J. Biol. Chem. 276(27):24871-80.