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Hunter Lab Hunter Lab People Publications Press Videos Links Contact Us Hunter Lab Molecular bases of growth control and cell cycle regulation Hunter Lab People Publications Press Videos Links Contact Us 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 Salk Institute celebrates 50th anniversary and renewal of National Cancer Institute designation Dec 07, 2023 LA JOLLA—The Salk Institute marks 50 years as a National Cancer Institute (NCI)-Designated Cancer Center with good news: NCI has renewed the designation and grant support for another five years. Read more » Three Salk scientists among 2022 Curebound Discovery Grant winners Oct 19, 2022 LA JOLLA—The Salk Institute’s American Cancer Society Professor Tony Hunter, Professor Reuben Shaw, and Assistant Professor Graham McVicker are among 12 inaugural 2022 Discovery Grant winners. The awards, which total $3 million, were launched this year by Curebound, a philanthropic organization dedicated to funding collaborative cancer research that has the potential to reach the clinic. Read more » Salk scientist Tony Hunter receives 2022 AACR Lifetime Achievement Award in Cancer Research Mar 24, 2022 LA JOLLA—Salk Institute Professor Tony Hunter will receive the 2022 American Association for Cancer Research (AACR) Award for Lifetime Achievement in Cancer Research at the April annual meeting of AACR, the largest cancer research organization in the world dedicated to preventing and curing all cancers. This major award is a significant recognition of Hunter’s contributions to cancer research, which have led to the development of the highly effective leukemia drug GleevecTM. Read more » The Lustgarten Foundation and Salk Institute announce strategic pancreatic cancer research partnership Feb 14, 2022 LA JOLLA/NEW YORK—The Lustgarten Foundation and Salk Institute today announced a new strategic partnership supported by a $5 million grant and focused on identifying and validating potential targets for new pancreatic cancer drugs. The effort will be led by four co-principal investigators, all prominent cancer researchers in the Salk Dedicated Program in Pancreatic Cancer: Professors Reuben Shaw, Ronald Evans, Tony Hunter and Assistant Professor Dannielle Engle. The partnership is part of the Lustgarten Advancing Breakthrough Science (LABS) Program. Read more » Salk team reveals never-before-seen antibody binding, informing both liver cancer and antibody design Feb 17, 2021 LA JOLLA—In structural biology, some molecules are so unusual they can only be captured with a unique set of tools. That’s precisely how a multi-institutional research team led by Salk scientists defined how antibodies can recognize a compound called phosphohistidine—a highly unstable molecule that has been found to play a central role in some forms of cancer, such as liver and breast cancer and neuroblastoma. Read more » Salk researchers accelerate, expand COVID-19 research Jun 29, 2020 LA JOLLA—As the COVID-19 pandemic continues across the globe, the Salk Institute joins in efforts to understand the fundamental science behind the novel coronavirus to pave the way to treatments and cures. COVID-19 exploits a vulnerability in the immune system’s armor: because the SARS-CoV-2 virus—the novel coronavirus that causes COVID-19—appeared in humans recently, our immune systems have no experience with the virus—and sometimes have difficulty fighting it. Read more » Mysterious tuft cells found to play role in pancreatitis Apr 17, 2020 LA JOLLA—Persistent inflammation of the pancreas (chronic pancreatitis) is a known risk factor for developing pancreatic cancer, the third-deadliest cancer in the United States. Tuft cells—cells sensitive to chemical (chemosensory) changes typically found in the intestines and respiratory tract—had previously been discovered in the pancreas, but their function has largely remained a mystery. Now, a team of Salk scientists led by Professor Geoffrey Wahl and Staff Scientist Kathleen DelGiorno has uncovered the formation of tuft cells during pancreatitis and the surprising role of tuft cells in immunity, using mouse models of pancreatitis. The findings, published in Frontiers in Physiology on February 14, 2020, could lead to the development of new biomarkers to test for pancreatitis and pancreatic cancer. Read more » Salk Institute hits play on new podcast series Oct 30, 2019 LA JOLLA—A new podcast series called Where Cures Begin launches this week and features one-on-one conversations with Salk researchers working at the forefront of their respective scientific fields, from cancer and neuroscience to plant biology, circadian science and more. The eight episodes of season 1, which will be released weekly beginning October 30, 2019, include interviews with the following Salk scientists: Read more » Salk scientist Tony Hunter receives National Cancer Institute Outstanding Investigator Award Oct 09, 2019 LA JOLLA, CA—Salk scientist Tony Hunter has received a National Cancer Institute (NCI) Outstanding Investigator Award (OIA), which supports accomplished leaders in cancer research. Hunter, who is an American Cancer Society Professor, will receive more than $7,500,000 over the next seven years to further his work. According to the NCI, the award supports investigators who are providing...