PHAS-I as a Link Between Mitogen-Activated Protein Kinase and Translation Initiation

• Published in: Science (American Association for the Advancement of Science) Vol. 266; no. 5185; pp. 653 - 656
• Main Authors: Lin, Tai-An, Kong, Xianming, Timothy A. J. Haystead, Pause, Arnim, Belsham, Graham, Sonenberg, Nahum, Lawrence, John C.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 28-10-1994; American Association for the Advancement of Science
• Subjects: 3T3 Cells; Adipocytes; Adipocytes - metabolism; Animals; Antibodies; Antiserum; Awards; Biological and medical sciences; Carrier Proteins; Cell physiology; Fundamental and applied biological sciences. Psychology; Growth factors; Homogenization; Insulin; Insulin - pharmacology; Mice; Mitogen-Activated Protein Kinase 1; Molecular and cellular biology; Peptide Initiation Factors - isolation & purification; Peptide Initiation Factors - metabolism; Phosphoproteins - metabolism; Phosphorylation; Physiological aspects; Protein Biosynthesis; Protein synthesis; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - metabolism; Proteins; Rats; Recombinant Proteins - metabolism; Resins; Serine - metabolism; Signal transduction; Synthesis; Adipocyte; Pancreatic hormone; Phosphorylation; Rat; Transferases; Initiation factor eIF4E; Rodentia; Translation initiation; In vitro; Insulin; Binding protein; Signal transduction; Vertebrata; Cell line; Mammalia; Protein synthesis; Growth factor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7939721

PHAS-I is a heat-stable protein (relative molecular mass $\approx$12,400) found in many tissues. It is rapidly phosphorylated in rat adipocytes incubated with insulin or growth factors. Nonphosphorylated PHAS-I bound to initiation factor 4E (eIF-4E) and inhibited protein synthesis. Serine-64 in PHAS-I was rapidly phosphorylated by mitogen-activated (MAP) kinase, the major insulin-stimulated PHAS-I kinase in adipocyte extracts. Results obtained with antibodies, immobilized PHAS-I, and a messenger RNA cap affinity resin indicated that PHAS-I did not bind eIF-4E when serine-64 was phosphorylated. Thus, PHAS-I may be a key mediator of the stimulation of protein synthesis by the diverse group of agents and stimuli that activate MAP kinase.