COMPLEX BETWEEN DIFFERENTLY PHOSPHORYLATED KINASE DOMAIN OF FGFR1 AND TAMDEN SH2

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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. Structures of differently phosphorylated kinase domain of FGFR1 will give better understanding of intermediate states of FGFR1 activation. To get more information, I try to co-crystallize activated kinase domain with a natural substrate, a domain construct containing two Src Homology domain (SH2) and C-terminal extension of Phospholipase C gamma (PLCg). This binds to phosphorylated tyrosine 766 (pY766) of kinase and its tyrosine 781 (Y781) on C-terminal extension is phosphorylated by kinase in trans. These structures will bring elucidation of phosphorylation mechanism of FGFR1 and give more opportunities to explore the downstream signaling pathways through binding mode between substrate and kinase.