Phage display in proteolysis and signal transduction.
The power of the phage display technology relies on the coupling of the functional display of combinatorial peptide or protein libraries with the ability of each member in the library to self-replicate and, at the same time, to encode the primary structure of the displayed polypeptide in its genome. Phage display systems, therefore, reflect the principle of encoded combinatorial chemistry close to perfection. Phage display libraries have extensively been used for the selection of peptides, antibody combining sites or protein variants binding to given structures such as polypeptides, carbohydrates, nucleic acids or small molecular weight compounds. The use of peptide libraries in selecting molecular interaction partners was extensively described in numerous publications and was subject to a variety of review articles in the past. More recently, and in the focus of this review, combinatorial phage libraries have been employed to examine substrate recognition in catalysis and signal transduction. The sensitivity and versatility of phage display for probing molecular recognition and catalysis by enzymes was demonstrated inasmuch as discriminating peptide substrates could be identified for even closely related proteases or tyrosine kinases. Furthermore, the modification of whole phage libraries by tyrosine kinases led to the identification of phosphopeptides specific for Src-homology-2 (SH2)- and phosphotyrosine-binding (PTB) domains, which are both structural and functional modules facilitating substrate recognition by protein kinases, phosphatases or adapter molecules involved in signal transduction.
Novartis Pharma AG, Arthritis and Bone Metabolism, Basel, Switzerland.
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D000595:Amino Acid Sequence; D001435:Bacteriophages / Q000235:genetics*; D003001:Cloning, Molecular; D006868:Hydrolysis; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018909:src Homology Domains
D011505:Protein-Tyrosine Kinases