Kermit L. Carraway

Professor of Cell Biology and Biochemistry

Ph.D. (1966) University of Illinois

Glycoprotein complexes

215 Papanicolaou Building, 1550 NW 10th Ave

Telephone: (305)243-6512
FAX: (305)243-4431

kcarrawa@med.miami.edu

Research Interests:

My primary research effort focuses on a glycoprotein complex, called Muc4 or sialomucin complex (SMC). This glycoprotein is a heterodimer composed of mucin and transmembrane subunits. The latter has two growth factor-like domains. Thus, Muc4 can contribute to two major attributes of epithelial cells and cancer cells, adhesiveness (anti-adhesive) and cell signaling. One of the growth factor domains serves as the only known ligand for the receptor tyrosine kinase ErbB2/HER2/Neu, an intramembrane ligand that can trigger ErbB2 phosphorylation and regulate its localization in epithelial cells.

By these mechanisms Muc4 acts as a modulator of an ErbB2 signaling switch, which helps to determine cell fate. In one switch mode a Muc4/ErbB2 complex acts as an intrinsic survival factor and promotes differentiation of epithelial cells. In the second mode Muc4 associates with an activated ErbB2 and other receptors in a multimeric complex to amplify proliferation signals, which can contribute to repair of epithelial damage. This latter mode can also contribute to the autonomous growth of cancers in cells which have already been neoplastically transformed. In this mode the Muc4 is acting as a “tumor progressor”. Both of these mechanisms are regulated by factors which control the expression of the Muc4 in the epithelia and tumors.

Our current research uses multiple model systems to investigate the functions and regulation of Muc4: mammary epithelial and cancer cells to determine its regulation and function in mammary development and neoplasia; corneal epithelial cells to determine its role in corneal differentiation, wound healing and the tear film; and airway epithelial cells to investigate its function, regulation and response to noxious agents which injure the airway. We also use mammalian cell culture and insect cell model systems and transgenic animals for investigations of the mechanisms by which Muc4 contributes to cell signaling. Finally, we are interested in the development of agents which can be used in diagnosis, prognosis or therapy for cancers or other diseases to which Muc4 contributes.

Representative Publications:

Carraway, K.L., Ramsauer, V.P., Haq, B. and Carraway, C.A.C. 2003. Cell signaling through membrane mucins. BioEssays 25, 66-71.

Soto, P., Price-Schiavi, S.A. and Carraway, K.L. 2003. SMAD2 and SMAD7 involvement in the post-translational regulation of Muc4 via the transforming growth factor-beta and interferon-gamma pathways in rat mammary epithelial cells. J. Biol. Chem. 278, 20338-20344.

Ramsauer, V.P., Carraway, C.A.C., Salas, P.J.I. and Carraway, K.L. 2003. Muc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cells. J. Biol. Chem. 278, 30142-30147.

Perez, A., Barco, R., Fernandez, I., Price-Schiavi, S A. and Carraway, K.L. 2003. PEA3 transactivates the Muc4/sialomucin complex promoter in mammary epithelial and tumor cells. J. Biol. Chem. 278, 36942-36952.

Lomako, J., Lomako, W., Carraway, C.A.C. and Carraway, K.L. 2005. Non-apoptotic desquamation of cells from corneal epithelium: putative role for Muc4/sialomucin complex in cell release and survival. J Cell Physiol 202: 115-124.

Rong, M., Rossi, E.A., Zhang, J., McNeer, R.R., Van Den Brande, J.M.H., Yasin, M., Weed, D. T., Carraway, C.A.C., Thompson, J. F. and Carraway, K.L. 2005. Expression and Localization of Muc4/Sialomucin Complex (SMC) in the Adult and Developing Rat Intestine: Implications for Muc4/SMC Function. J. Cell. Physiol. 202: 275-284.

Nagy, P., Friedländer, E., Tanner, M., Kapanen, A.I., Carraway, K.L., Isola, J. and Jovin, T.M. 2005. Decreased accessibility and lack of activation of erbB2 in a Herceptin-resistant, MUC-4-expressing breast cancer cell line. Cancer Res. 65: 473-482.  

Ramsauer, V.P., Pino, V., Farooq, A., Carraway, C.A.C., Salas, P.J.I. and Carraway, K.L. 2006.Muc4-ErbB2 complex formation and signaling in polarized CACO-2 epithelial cells indicate that Muc4 acts as an unorthodox ligand for ErbB2. Mol. Biol. Cell 17: 2931-2941.
Pino, V., Ramsauer, V.P., Salas, P., Carraway, C.A.C. and Carraway, K.L. 2006. Membrane mucin Muc4 induces density dependent changes in Erk activation in mammary epithelial and tumor cells: Role in reversal of contact inhibition. J. Biol. Chem. 281: 29411-29420.