Protein tyrosine kinase-substrate interactions.
Protein tyrosine kinases (PTKs) are enzymes that catalyze the phosphorylation of tyrosyl residues. They are important in physiological and pathophysiological processes. Protein substrates of PTKs are often difficult to discern, but recently reported methods have helped to identify targets and characterize their structural interactions with kinases. A mechanism-based bisubstrate analog strategy has given X-ray crystallographic insights into how several topical PTKs, including the insulin receptor, Abl and epidermal growth factor receptor, interact with tyrosine-containing peptide substrates. These PTK co-crystal structures reveal both conserved and specialized features of recognition that probably contribute to substrate selection and the individual functions of these key enzymes.
Bose
Ron
R
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Holbert
Marc A
MA
Pickin
Kerry A
KA
Cole
Philip A
PA
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D040081:Protein Array Analysis; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D016315:Proto-Oncogene Proteins c-abl