The rockefeller university

Event Details

Type

Friday Lecture Series

Speaker(s)

John Kuriyan, Ph.D., professor, department of molecular and cell biology and department of chemistry, University of California, Berkeley; investigator, Howard Hughes Medical Institute

Speaker bio(s)

The epidermal growth factor receptor (EGFR) and its relatives, Her2, Her3, and Her4 play important roles in cell growth and differentiation and are misregulated in numerous cancers. The binding of growth factors to these receptors induces the dimerization and activation of their cytoplasmic kinase domains, resulting in the phosphorylation of tyrosine residues in their C-terminal tails and recruitment of downstream effectors. Ligand binding causes a conformational change that enables dimerization, with the dimer interface mediated entirely by the receptor. These findings suggested that EGFR might be activated by a mechanism shared by many other receptor tyrosine kinases, in which ligand-induced dimerization brings the kinase domains close enough together to activate each other through transphosphorylation. But, unexpectedly, some years ago Dr. Kuriyan's laboratory discovered that the catalytic domain is activated by the formation of an asymmetric dimer in which one kinase domain, the "activator," acts as an allosteric activator for a second "receiver" kinase domain. This activation mechanism resembles the activation of cyclin-dependent kinases by cyclins, with the EGFR kinase domain acting as its own "cyclin." More recently, Dr. Kuriyan's laboratory has focused on the nature of the coupling of the extracellular domain through the TM-JM segment to the kinase domain and the mechanism of tail phosphorylation, the most important outcome of receptor activation. These questions are especially intriguing in light of the fact that distinct tyrosine phosphorylation sites recruit signaling proteins with entirely different roles in the signaling pathway, with some being downstream effectors, while others exert feedback inhibition on the receptor. Dr. Kuriyan will describe his current studies aimed at uncovering answers to these questions.

 

Dr. Kuriyan received his Ph.D. from MIT in 1986, and did postdoctoral work at Harvard University. In 1987, he joined Rockefeller, becoming a professor in 1993. Since 2001, he has been a professor of molecular and cell biology and also of chemistry at the University of California, Berkeley. He became an investigator of the Howard Hughes Medical Institute in 1990. Dr. Kuriyan's research is concerned with the atomic-level description of molecular mechanisms pertaining to mammalian cell signaling and DNA replication. In addition to being a foreign member of The Royal Society, he is a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Sciences.

Open to

Public

Host

Roderick MacKinnon, M.D.

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Linda Hanssler

Phone

(212) 327-7714

Sponsor

Linda Hanssler
(212) 327-7714
lhanssler@rockefeller.edu

Readings

http://librarynews.rockefeller.edu/?p=3962