New Delhi, June 28 Researchers at the Indian Institute of Science Education and Research (IISER), Kolkata, have identified a Vascular Endothelial Growth Factor Receptor (VEGFR) that can pave the way for developing medical treatments for colon and renal cancers.
The VEGFR family of receptors is the key regulator of the process of generating new blood vessels essential for functions like embryonic development, wound healing, tissue regeneration, and tumour formation.
Targeting VEGFRs can help in the treatment of various malignant and non-malignant diseases.
In the study, the researchers said that they were intrigued by the fact that two members of the family VEGFR 1 and VEGFR 2 behaved quite differently.
“While VEGFR 2, the primary receptor regulating process of formation of new blood vessels, could be spontaneously activated, without its ligand, the other member of the family VEGFR 1 cannot be spontaneously activated even when overexpressed in cells,” said Dr. Rahul Das from the Department of Biological Sciences, along with other researchers, in the paper published in the journal Nature Communication.
“It camouflages as a dead enzyme VEGFR1 and binds with ten-fold higher affinity to its ligand VEGF-A than VEGFR2. This ligand binding induces a transient kinase (speeding up chemical reactions in the body by an enzyme) activation,” they added.
Activation of VEGFR1 has been found to lead to cancer-associated pain, tumour cell survival in breast cancer, and migration of human colorectal cancer cells.
Probing why one member of the VEGFR family is so spontaneously activated and the other autoinhibited, the team found a unique ionic latch, present only in VEGFR1.
It “keeps kinase autoinhibited in the basal state. The ionic latch hooks the juxtamembrane segment onto the kinase domain and stabilises the autoinhibited conformation of VEGFR1,” the researchers explained.
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