Stevan R. Hubbard

Professor, Skirball Institute of Biomolecular Medicine, Structural Biology. Department of Biochemistry and Molecular Pharmacology. Coord Structural Biology Program

Ph.D., 1987 Stanford University

Keywords: Insulin receptor, Jak2, MuSK, Protein tyrosine kinase, X-ray crystallography

 

Contact Information: 

Skirball Institute of Biomolecular Medicine
540 First Avenue 3rd floor, Lab 4
New York, N.Y. 10016
Office Tel: (212) 263-8938
Lab Tel: (212) 263-8968
Fax: (212) 263-8951
E-mail: stevan.hubbard@med.nyu.edu

Administrative Contact:

Anne Ng
Tel: (212) 263-8573
Email: anne.ng@nyumc.org


Structural and Mechanistic Studies of Protein Tyrosine Kinases

My laboratory is interested in the molecular mechanisms by which the insulin receptor and other receptor tyrosine kinases (RTKs) are activated upon ligand binding, and the structural basis for recruitment of downstream signaling proteins to activated receptors. The main experimental technique we employ for three-dimensional structure determination is x-ray crystallography. Members of the RTK family include, among others, the insulin and insulin-like growth factor-1 (IGF1) receptors, fibroblast growth factor receptor, platelet-derived growth factor receptor, and epidermal growth factor receptor. RTKs play critical roles in signal transduction pathways that mediate cell proliferation, differentiation, migration and metabolism, both in organismal development and in adult homeostasis. RTKs have also been implicated in the onset or progression of numerous cancers. We are also studying the molecular mechanisms by which Jak2, a member of the Janus kinase family of non-receptor tyrosine kinases, is regulated. Activating mutations in Jak2 are causative for myeloproliferative neoplasms in humans.

Selected Publications:

Wu, J., Li, W., Craddock, B.P., Foreman, K.W., Mulvihill, M.J., Ji, Q., Miller, W.T., and Hubbard, S.R. Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor. EMBO J. 27, 1985-1994 (2008). PMID: 18566589

Depetris, R.S., Wu, J., and Hubbard, S.R. Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14. Nat. Struct. Mol. Biol. 16, 833-839 (2009). PMID: 19648926

Bergamin, E., Hallock, P.T., Burden, S.J, and Hubbard, S.R. The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization. Mol. Cell 38, 100-109 (2010). PMID: 20603078

Ungureanu, D., Wu, J., Pekkala, T., Niranjan, Y., Young, C., Jensen, O.N., Xu, C.F., Neubert, T.A., Skoda, R.C., Hubbard, S.R., and Silvennoinen, O. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat. Struct. Mol. Biol. 18, 971-976 (2011). PMID: 21841788

Bandaranayake, R.M., Ungureanu, D., Shan, Y., Shaw, D.E., Silvennoinen, O., and Hubbard, S.R. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nat. Struct. Mol. Biol. 19, 754-759 (2012). PMID: 22820988

Click here to see all publications in PubMed