Research Links Enzymes to Proteins in Cells

Study Title: An atlas of substrate specificities for the human serine/threonine kinome

Publication: Nature(Online) January 11, 2023 https://www.nature.com/articles/s41586-022-05575-3

Dana-Farber Cancer Institute author: Lewis C. Cantley, PhD

Summary:

Thousands of proteins in a human cell are regulated by phosphorylation — the addition of small chemical groups to the proteins’ amino acids by enzymes called protein kinases. This process is known as phosphorylation. Abnormal protein phosphorylation has been implicated in a number of diseases, notably cancer and degenerative diseases like Parkinson’s and Alzheimer’s. Some 90,000 sites of phosphorylation on serine and threonine amino acids have been identified, but it hasn’t been known which of more than 300 protein serine or threonine kinases are responsible. In a new study, researchers at Weill Cornell Medicine and Dana-Farber Cancer Institute purified and characterized the substrate specificity of essentially all the human protein-serine/threonine kinases and developed a computational method to identify the kinases capable of phosphorylating every known phosphorylation site in the human serine/threonine proteome.

Impact:

Several thousand sites of serine and threonine phosphorylation have been associated with human diseases, including cancers and diabetes. The new study provides a mechanism for rapidly identifying the protein kinase that is driving the abnormal behavior of individual cancers. Since many drugs for inhibiting protein kinases are already approved or in clinical trials, this information can rapidly lead to a new therapy that can be individualized to the patient.

Funding:

The research was supported by the Leukemia & Lymphoma Society and grants from the National Institutes of Health; the Cancer Research UK and Brain Tumor Charity; the Charles and Marjorie Holloway Foundation, and the MIT Center for Precision Cancer Medicine.

/Public Release. This material from the originating organization/author(s) may be of a point-in-time nature, edited for clarity, style and length. The views and opinions expressed are those of the author(s).View in full here.