New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017 by Brian Wallheimer, Purdue University

Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

Kinases are proteins that catalyze the transfer of a phosphate group to another , a process called phosphorylation that is key to a protein's function. Many phosphorylated proteins are oncogenes, ones that can trigger the formation of .

There are dozens of kinase inhibitors on the market used to treat cancer. But cancer cells adapt, making some drugs less effective. New kinase targets would lead to new drugs that could diversify treatment options for patients with hard-to-treat cancers, a long and tedious process.

"These are the critical molecules for cancer growth and proliferation," said W. Andy Tao, Purdue professor of biochemistry and the senior author of the findings published in the journal ACS Central Science. "It's important to know all the alternative kinases that can phosphorylate an oncogene, so if we see resistance, we re-target it."

Previously there was no existing method available to systematically identify kinases responsible for phosphorylating an oncogene. Tao and collaborators from Purdue's Department of Medicinal Chemistry and Molecular Pharmacology (MCMP), Department of Chemistry, and the Purdue Center for Cancer Research developed a powerful method that can rapidly screen for -protein interactions. Tao and his collaborator, Chang-Deng Hu, professor of MCMP, met and devised the idea during a scientific retreat, but it took them several years to finally work out the technical details.

The method utilizes a known imaging assay called bimolecular fluorescence complementation (BiFC) in which a fluorescent protein is split into two pieces, labeled terminals N and C. One terminal is added to a suite of kinases, and the other is placed with a target oncogene.

"If the two proteins interact with each other, they will pull the N and C terminals together, and an intact fluorescent protein can be reconstituted to emit the fluorescent light." Hu said.

Connected proteins are visible because of the fluorescence, but scientists can use the rapid mass spectrometry to identify the kinases. Researchers tested their method on a library of 559 human kinases and were able to identify new kinases against the library and confirm them through other biochemical assays.

Tao said the method they reported here integrates two cutting-edge biochemical techniques to enable successful identification of potential protein kinases of substrates (e..g, oncogenic proteins). The is universal and can be used for the screening of novel protein kinases of any protein substrate. For the next step, they are working with proteins involved in late-stage development. Most of their kinases are not known.

Explore further: Map of substrate-kinase interactions may lead to more effective cancer drugs

More information: I-Hsuan Chen et al. Phosphoproteins in extracellular vesicles as candidate markers for breast cancer, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1618088114

Related Stories

Map of substrate-kinase interactions may lead to more effective cancer drugs

March 27, 2012
(Medical Xpress) -- Later-stage cancers thrive by finding detours around roadblocks that cancer drugs put in their path, but a Purdue University biochemist is creating maps that will help drugmakers close more routes and ...

Researchers mapped interactions of key group of human proteins, the protein phosphatases

March 15, 2017
Coordinated activities of protein kinases and protein phosphatases ensure phosphorylation homeostasis and amplitude of signaling response, and understandably its imbalance is linked to diseases, such as cancer. Unlike with ...

New role of protein kinases in embryo development and cancer

January 7, 2016
A group of protein kinases have been found to play an important role in embryo development and may even be a potential cancer drug target, says research led by Queen Mary University of London (QMUL) and the Francis Crick ...

New drug compounds could provide non-toxic, effective way to inhibit enzymes that cause cancers

April 25, 2017
Drug compounds being developed at Purdue University could effectively target and inhibit protein kinase enzymes and secondary mutated versions that drive multiple types of cancers. The compounds are non-toxic compared to ...

Recommended for you

New drugs are improving survival times for patients with aggressive type of blood cancer, study finds

June 25, 2018
Survival times for a highly aggressive type of blood cancer have nearly doubled over the last decade due to the introduction of new targeted drugs, a Yorkshire study has shown.

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.