A Princeton University-led research team has discovered that protein competition over an important enzyme provides a mechanism to integrate different signals that direct early embryonic development. The work suggests that these signals are combined long before they interact with the organism's DNA, as was previously believed, and also may inform new therapeutic strategies to fight cancer.
The fought-over enzyme, known as the mitogen-activated protein kinase (MAPK), is found in all complex organisms, ranging from yeast to humans. MAPK signaling pathways, or chemical networks that involve the enzyme, are critical for normal development, and defects in these pathways can lead to severe developmental disorders and cancer.
During early embryonic development, a single undifferentiated cell becomes a complex and highly specialized organism containing a variety of different cell types arranged in very precise patterns. These patterns, which ensure that the body structures from head-to-tail and front-to-back develop correctly and in the appropriate places, are created when cells respond to a series of chemical signals from different signaling pathways. The different patterning signals received by any given cell are ultimately combined to govern its future fate and tell it what kind of cell it should become.
Until now, scientists believed these pathways operated largely independently of one another to produce protein signals that traveled to the nuclei of the embryo's cells where DNA is stored. There, coordination of these signals was thought to occur when they interacted with cell DNA to influence and control the expression of genes. Results published March 9 in the journal Current Biology, however, suggest that competition for the MAPK enzyme among proteins in different pathways influences which signals are sent to cells, establishing a biochemical mode of signal integration that adds a previously unrecognized layer of complexity
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