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Science 11 June 1993: Vol. 260. no. 5114, pp. 1658 - 1661 DOI: 10.1126/science.8503013
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Articles
Science, Vol 260, Issue 5114, 1658-1661
Copyright © 1993 by American Association for the Advancement of Science
Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase
SA Moodie,
BM Willumsen,
MJ Weber,
and
A Wolfman
Department of Cell Biology, Cleveland Clinic Foundation, OH 44106.
The guanosine triphosphate (GTP)-binding protein Ras functions in regulating growth and differentiation; however, little is known about the protein interactions that bring about its biological activity. Wild-type Ras or mutant forms of Ras were covalently attached to an insoluble matrix and then used to examine the interaction of signaling proteins with Ras. Forms of Ras activated either by mutation (Gly12Val) or by binding of the GTP analog, guanylyl-imidodiphosphate (GMP-PNP) interacted specifically with Raf-1 whereas an effector domain mutant, Ile36Ala, failed to interact with Raf-1. Mitogen-activated protein kinase (MAP kinase) activity was only associated with activated forms of Ras. The specific interaction of activated Ras with active MAP kinase kinase (MAPKK) was confirmed by direct assays. Thus the forming of complexes containing MAPKK activity and Raf-1 protein are dependent upon the activity of Ras.
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- The hsp90-binding Antibiotic Geldanamycin Decreases Raf Levels and Epidermal Growth Factor Signaling without Disrupting Formation of Signaling Complexes or Reducing the Specific Enzymatic Activity of Raf Kinase.
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Development
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- The Renaturable 69-and 63-kDa Protein Kinases That Undergo Rapid Activation in Chemoattractant-stimulated Guinea Pig Neutrophils Are p21-Activated Kinases.
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- Different Effects of Various Phospholipids on Ki-Ras-, Ha-Ras-, and Rap1B-induced B-Raf Activation.
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271, 14680-14683
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- Identification of an Essential Signaling Cascade for Mitogen-activated Protein Kinase Activation by Angiotensin II in Cultured Rat Vascular Smooth Muscle Cells. POSSIBLE REQUIREMENT OF Gq-MEDIATED p21ras ACTIVATION COUPLED TO A Ca2+/CALMODULIN-SENSITIVE TYROSINE KINASE.
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