The VEGFR family of receptors is a key regulator of the process of forming new blood vessels essential for functions such as embryonic development, wound healing, tissue regeneration, and tumor formation.
Targeting VEGFR may help in the treatment of various malignant and non-malignant diseases.
In the study, the researchers said they were surprised by the fact that the two family members, VEGFR1 and VEGFR2, behaved quite differently.
Dr. Rahul Das said, "While VEGFR2, the primary receptor regulating the process of new blood vessel formation, can be activated spontaneously without its ligand, the other member of the family, VEGFR1, is highly activated in cells. Cannot be activated automatically even if activated." from the Department of Biological Sciences, along with other researchers, in a paper published in the journal Nature Communications.
“It hides as a dead enzyme, VEGFR1, and binds to its ligand VEGF-A with ten times greater affinity than VEGFR2. This ligand binding induces a transient kinase (an enzyme that accelerates chemical reactions in the body) activation,” he said.
Activation of VEGFR1 has been found to cause cancer-associated pain, tumor cell survival in breast cancer, and migration of human colorectal cancer cells.
Investigating why one member of the VEGFR family is so readily activated and another is spontaneously inhibited, the team found a unique ionic latch that is present only in VEGFR1.
This "keeps the kinase autoinhibited in the basal state." The ionic latch connects the juxtamembrane segment to the kinase domain and stabilizes the autoinhibited conformation of VEGFR1,” the researchers explained.
Targeting VEGFR may help in the treatment of various malignant and non-malignant diseases.
In the study, the researchers said they were surprised by the fact that the two family members, VEGFR1 and VEGFR2, behaved quite differently.
Dr. Rahul Das said, "While VEGFR2, the primary receptor regulating the process of new blood vessel formation, can be activated spontaneously without its ligand, the other member of the family, VEGFR1, is highly activated in cells. Cannot be activated automatically even if activated." from the Department of Biological Sciences, along with other researchers, in a paper published in the journal Nature Communications.
“It hides as a dead enzyme, VEGFR1, and binds to its ligand VEGF-A with ten times greater affinity than VEGFR2. This ligand binding induces a transient kinase (an enzyme that accelerates chemical reactions in the body) activation,” he said.
Activation of VEGFR1 has been found to cause cancer-associated pain, tumor cell survival in breast cancer, and migration of human colorectal cancer cells.
Investigating why one member of the VEGFR family is so readily activated and another is spontaneously inhibited, the team found a unique ionic latch that is present only in VEGFR1.
This "keeps the kinase autoinhibited in the basal state." The ionic latch connects the juxtamembrane segment to the kinase domain and stabilizes the autoinhibited conformation of VEGFR1,” the researchers explained.
