Analyzing the roles of multi-functional proteins in cells: The case of arrestins and GRKs.

Gurevich VV, Gurevich EV
Crit Rev Biochem Mol Biol. 2015 50 (5): 440-52

PMID: 26453028 · PMCID: PMC4852696 · DOI:10.3109/10409238.2015.1067185

Most proteins have multiple functions. Obviously, conventional methods of manipulating the level of the protein of interest in the cell, such as over-expression, knockout or knockdown, affect all of its functions simultaneously. The key advantage of these methods is that over-expression, knockout or knockdown does not require any knowledge of the molecular mechanisms of the function(s) of the protein of interest. The disadvantage is that these approaches are inadequate to elucidate the role of an individual function of the protein in a particular cellular process. An alternative is the use of re-engineered proteins, in which a single function is eliminated or enhanced. The use of mono-functional elements of a multi-functional protein can also yield cleaner answers. This approach requires detailed knowledge of the structural basis of each function of the protein in question. Thus, a lot of preliminary structure-function work is necessary to make it possible. However, when this information is available, replacing the protein of interest with a mutant in which individual functions are modified can shed light on the biological role of those particular functions. Here, we illustrate this point using the example of protein kinases, most of which have additional non-enzymatic functions, as well as arrestins, known multi-functional signaling regulators in the cell.

MeSH Terms (13)

Animals Arrestins Enzyme Activation G-Protein-Coupled Receptor Kinases Gene Knockdown Techniques Gene Knockout Techniques Humans Ligands Models, Molecular Mutant Proteins Protein Conformation Recombinant Proteins Signal Transduction

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