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The biologic effects of a diverse variety of polypeptide
growth factors are mediated by cell surface receptors with intrinsic
protein tyrosine kinase activity. These receptors are  invoked at various
points in growth and development, and also play critical roles in tumorigenesis.
This laboratory is studying the
mechanisms of signal
transduction used by growth factor receptor/protein
tyrosine kinases. Recent evidence indicates that the binding of a growth
factor to its specific receptor results in the formation of a signal
transduction complex incorporating the receptor protein and various
intracellular signal-transducing proteins. The signal-transducing proteins
in the complex are activated, and multiple biochemical signals originate
from the signaling complex. Our goals are to understand the mechanisms
of receptor activation and signal transduction complex formation, and
to determine how these processes participate in aberrant (cancerous)
cell growth. In this context, two receptors are being examined: the
epidermal growth factor (EGF) receptor (HER1), and the ErbB3 receptor
protein (HER3), which is a recently identified member of the EGF receptor
family and is potentially involved in breast cancer cell growth.
Specific projects:
1. Biochemical and biophysical studies
of the EGF receptor protein tyrosine kinase.
2. Novel signaling targets of ErbB (HER) family
receptor proteins.
3. Signaling of ErbB (HER) receptors within membrane
microdomains (lipid rafts).
Representative Publications:
Lee, N.Y., Hazlett, T.L., and Koland, J.G.: Structure and dynamics of the epidermal growth factor receptor C-terminal phosphorylation domain. Protein Sci. 15:1142-1152, 2006.
Lee, N.Y., Koland, J.G.: Conformational changes accompany phosphorylation of the epidermal growth factor receptor C-terminal domain. Protein
Sci. 14:2793-2803, 2005.
Vijapurkar,
U., Kim, M.-S., and Koland, J.G. Roles of mitogen-activated protein
kinase and phosphoinositide 3'-kinase in ErbB2/ErbB3 coreceptor-mediated
heregulin signaling. Exp. Cell. Res. 284:291-302,
2003.
Hellyer,
N.J., Kim, M.-S., and Koland, J.G. Heregulin-dependent activation of
phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 coreceptor.
J. Biol. Chem. 276:42153-42161, 2001.
Click
here to see a list of additional publications
Center and Program affiliations:
Holden Comprehensive Cancer Center
Interdisciplinary
Graduate Program in Molecular Biology
Biosciences
Program
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