Salk Institute and SUGEN scientists map 'human kinome'

December 05, 2002

La Jolla, Calif.--A California research team has mapped an entire group of human enzymes, providing important information for the development of a new generation of drugs to treat cancer and other diseases. The findings will be published in the Dec. 6 issue of Science.

In the study, the team from the Salk Institute for Biological Studies and the biotechnology company SUGEN created a detailed catalog of the 518 protein kinase genes encoded by the human genome. Protein kinases are among the most important regulators of cell behavior. By chemically adding phosphate groups to other proteins, they control the activity of up to 30 percent of all cellular proteins, and are involved in almost all cellular functions. They are especially important in sending signals between and within cells, and in orchestrating complex functions such as cell division. Overactive kinases are the cause of some types of cancer, and the central role of kinases in controlling cell behavior has led to their being investigated as targets for treatment of a variety of other diseases, including diabetes, osteoporosis, inflammation and occular diseases.

Scientists in academia and pharmaceutical companies have intensively studied the role of kinases in basic biology and in disease for many years, and several drugs targeting kinases are under development. These drugs may offer an alternative treatment to standard chemotherapy for the treatment of specific kinds of cancer. The recently approved anti-cancer drug Gleevec™, which is proving successful in treating chronic myeloid leukemia, is the first example of a small molecule kinase inhibitor drug of this sort.

The Human Kinome Project, as the researchers have called the current study, will have broad implications in both the development of new drugs and the understanding of basic cellular biology. Not only does it add over 100 new kinases that were not previously studied, it also classifies and compares all human kinases with each other and with kinases from several other organisms, to better predict their function.

By identifying the full range of protein kinases in the human genome, the scientists from SUGEN and the Salk Institute have illuminated new possibilities for drug development. SUGEN, a South San Francisco-based biotechnology company, is owned by the Pharmacia Corporation and is focused on the discovery and development of novel drugs that target kinases.

"Kinase inhibitors will be major players in the next generation of targeted drugs for cancer and other diseases," said Tony Hunter, a Salk Institute professor of molecular and cell biology and one of the authors of the paper. "Ultimately, we'll be able to use this information for diagnostic and therapeutic purposes."

The SUGEN research team has been working for the past decade on nailing down the exact number of protein kinases, according to Sucha Sudarsanam, director of bioinformatics for Pharmacia and an author of the study. "We had a clear computational strategy for how to mine the human genome for protein kinases. And yet we didn't solely rely on automation. We manually went through each one of these sequences to confirm that the mapping process was accurate," he said.

Previous efforts to provide a comprehensive identification of protein kinases were incomplete, according to Sudarsanam. "We had incomplete sequence data in the past, and the real breakthrough came from the completion of the Human Genome Project," he said. With their latest findings, the SUGEN and Salk scientists have eliminated speculation about the number of protein kinases. "The total is about half that predicted 15 years ago by Hunter, but it is still a strikingly large number, constituting about 1.7 percent of all human genes," the researchers state in the Science paper.

Hunter began his seminal research on protein kinases in the late 1970s and is one of the scientists credited with discovering tyrosine kinases, one of the most important classes of kinases. He is encouraged by the culmination of the mapping process, but he is quick to point out that further research and development could take years before there are definitive new treatments.

"We know that the process of understanding human disease is very complicated, and that on average drug development takes 10 to 15 years." Hunter said. "But mapping the human kinome is clearly an important step, and we are very excited about the possibilities raised by this study."
-end-
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.

Salk Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.