CLASS III RECEPTOR TYROSINE KINASES THAT BIND HELICAL-BUNDLE LIGANDS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Transmembrane receptor defects/malfunctions frequently cause or contribute to cancer. Modulating these receptors holds promises for developing cancer therapies, but understanding how hormones/growth factors act through these receptors is required. KIT, the receptor for Stem Cell Factor (SCF), is essential for humans. Kit malfunctioning is associated with gastrointestinal stromal tumors, germ cell tumors and acute myeloid leukemia. Elucidating the interaction mechanism between KIT and SCF may provide avenues for developing strategies against KIT-related cancers. We propose to study the KIT/SCF interactions both structurally and functionally. Using X-ray diffraction, we are in progress of getting high-resolution atomic images of the KIT/SCF complex.