Credit: Bjorn Onfelt/Dan Davis
New research provides additional insight into how natural killer (NK) cells eliminate abnormal hematopoietic cells.
The investigators evaluated 2 molecules that are known to play important roles in this process.
Ewing’s sarcoma-associated transcript 2 (EAT-2) and signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) are expressed in NK cells, and their combined expression is essential for NK cells to kill abnormal hematopoietic cells.
“We knew that EAT-2 cooperates with SAP, and, with this research project, we wanted to better understand why they are both required for the proper functioning of NK cells,” said study author André Veillette, PhD, of the Institut de Recherches Cliniques de Montréal (IRCM) in Canada.
Dr Veillette and his colleagues described this research in the Journal of Experimental Medicine.
“We identified the molecular chain of events that occur and showed that EAT-2 and SAP perform different functions using distinct mechanisms,” Dr Veillette said. “These findings explain the cooperative and essential function of these 2 molecules in activating NK cells, thereby allowing them to kill abnormal blood cells.”
The investigators noted that SAP couples SLAM family receptors to the protein tyrosine kinase Fyn and the exchange factor Vav, thereby promoting conjugate formation between NK cells and target hematopoietic cells.
EAT-2, on the other hand, works by accelerating the polarization and exocytosis of cytotoxic granules toward hematopoietic cells.
EAT-2 mediates its effects in NK cells by linking SLAM family receptors to phospholipase Cγ, calcium fluxes, and Erk kinase. These signals are triggered by 1 or 2 tyrosines that are located in the carboxyl-terminal tail of EAT-2.
Dr Veillete pointed out that, although EAT-2 and SAP behave differently, both are linked to receptors of the SLAM family on the cell surface.
“Because they can make better drug targets, our future work will focus on these receptors,” he said, “which could eventually lead to identifying new potential treatment avenues for blood cancers such as leukemia and lymphoma.”
