Welcome to the Hunter lab

The goal of the Hunter Lab is to understand the molecular basis of cell growth control and cell cycle regulation. Many growth factor receptors are protein-tyrosine kinases (PTK), which are activated by ligand-induced dimerization. Mitogenic signalling by PTKs involves tyrosine phosphorylation of critical target proteins. We are currently investigating what signal pathways are activated by the mammalian PDGF and stem call factor receptor PTKs, and the EphA2 receptor PTK, and investigating the roles of the Nck and c-Cbl adaptor proteins that are phosphorylated by activated receptor PTKs. We are also studying what signalling pathways are stimulated when integrin receptors bind to extracellular matrix proteins, such as fibronectin, in mammalian cells. We are focusing on the roles of the focal adhesion kinase (FAK) nonreceptor PTK and its relative Pyk2, and the c-Src family of nonreceptor PTKs, which are activated upon adhesion. We have also identified a Drosophila FAK/Pyk2 homologue, DmFAK, and we are carrying out a genetic analysis of its function.

To complement our work on PTKs, we are investigating the functions of protein-tyrosine phosphatases (PTPs) in cell signalling. We are studying the receptor-like PTP, RPTPa, which like most RPTPs has a twin catalytic domain structure. The crystal structure of the membrane proximal catalytic domain of RPTPa shows that it exists as an inactive dimer, suggesting that dimerization of RPTPa, and other RPTPs, may negatively regulate their activity. We are have shown that this is true for the CD45 RPTP, and have evidence that RPTPa activity is also inhibited by dimerization. This principle of regulation would be the exact opposite of that observed for receptor PTKs.

Our studies on the role of phosphorylation in mammalian cell cycle regulation are focused on the cyclin-dependent kinases (Cdk), and their substrates and inhibitors, and on the Cdc7/Dbf4 kinase. Using a new protein kinase substrate screen, we have identified Prc1, a spindle-associated protein, as a Cdk substrate, and we have also shown that Cdc6, an essential component of the prereplication complex that is bound to chromosomal origins, is phosphorylated by cyclin E/Cdk2, resulting in its export from the nucleus thus preventing rereplication. We have identified a novel peptidyl-prolyl isomerase, Pin1, that contains a WW domain and a prolyl isomerase domain. Pin1 is the functional homologue of yeast Ess1p, a protein essential for progression through mitosis. We have solved the structure of Pin1, and shown that it binds to phosphorylated Ser.Pro sequences, which are generated by Cdk phosphorylation. We are studying the role of Pin1 in cell cycle progression.

News Highlights

Feb 14, 2017 – Salk scientist awarded inaugural Sjöberg Prize for cancer breakthrough [click to view]

Jul 12, 2016 – Power up: growing neurons undergo major metabolic shift [click to view]

Apr 26, 2016 – Tamping down neurons’ energy use could treat neurodegeneration [click to view]

Jul 02, 2015 – New technique maps elusive chemical markers on proteins [click to view]

Feb 04, 2015 – Tony Hunter wins BBVA Foundation Frontiers of Knowledge Award in Biomedicine [click to view]

Aug 05, 2014 – Salk researcher Tony Hunter to receive 2014 Royal Medal in biological sciences [click to view]

May 29, 2014 – Pedal the Cause funds local ground-breaking cancer research with inaugural grant awards [click to view]

Mar 25, 2013 – American Association for Cancer Research appoints Salk scientists to inaugural class of fellows [click to view]

Sep 25, 2012 – What can the water monster teach us about tissue regeneration in humans? [click to view]

Jun 09, 2011 – Salk Institute hosts Cell Cycle Symposium – Discussions that change lives [click to view]

Mar 02, 2010 – Salk Institute cancer researcher Tony Hunter named to Frederick W. and Joanna J. Mitchell Chair [click to view]

Dec 24, 2009 – Mobilizing the repair squad: Critical protein helps mend damaged DNA [click to view]

Aug 31, 2009 – Chemotherapy resistance: Checkpoint protein provides armor against cancer drugs [click to view]

Jun 24, 2009 – Climbing the ladder to longevity: critical enzyme pair identified [click to view]

Jan 02, 2008 – Breast cancer cells have to learn to walk before they can run [click to view]

Oct 30, 2007 – Get in Touch First [click to view]

May 22, 2007 – Tony Hunter receives Robert. J. and Claire Pasarow Award for Cancer Research [click to view]

Sep 11, 2006 – Distinguishing friend from foe in the battle against cancer [click to view]

Feb 07, 2006 – Genetically modified mice are resistant to obesity despite a high fat diet [click to view]

Apr 07, 2005 – Molecular ‘zipcode’ guides nerves to correct places in body [click to view]

Jan 14, 2005 – Salk Scientist who discovered cancer ‘switch’ awarded the Wolf Prize in Medicine [click to view]

Dec 03, 2004 – Salk Scientist Who Revolutionized Cancer Research Awarded Horwitz Prize [click to view]

Nov 08, 2004 – Salk Institute Scientist Tony Hunter Named to Institute of Medicine [click to view]

Mar 02, 2004 – Hunter Receives Two Major Cancer Awards [click to view]

Sep 29, 2003 – Salk Researchers Ranked in Top 25 of Scientific Citations Worldwide [click to view]

Jul 31, 2003 – Missing Enzyme Found to Lead to Alzheimer?s Disease Symptoms [click to view]

Dec 05, 2002 – Salk Institute and SUGEN Scientists Map ‘Human Kinome’ [click to view]

Jan 31, 2000 – Potential Male Contraceptive Target Discovered by Salk Scientists [click to view]