Structural and functional properties of ras proteins.
The ras proteins belong to a family of related polypeptides that are present in all eukaryotic organisms from yeast to human. Their extraordinary evolutionary conservation suggests that they have essential cellular functions, although their exact role remains unknown. Mutations in specific amino acids and overexpression of normal proteins have been linked to altered proliferation and/or differentiation and, particularly, to neoplastic processes. Mature ras proteins are located on the inner side of the plasma membrane, and their biochemical properties include binding and exchange of guanine nucleotides and GTPase activity. The favored hypothesis for ras function is that these proteins exist in an equilibrium between an inactive conformation (p21.GDP) and an active conformation (p21. GTP) in which they are able to interact with their as yet unknown cellular target or targets. Similarities in cellular location, structure, and biochemistry with other known regulatory (G) proteins suggest that they play a role in transduction of signals from the cell surface. The elucidation of the crystal structure of normal and transforming ras proteins and the identification of cellular proteins that interact directly with them (GAP, CDC25) or suppress some of their biological effects (Krev-1) have opened new avenues in the search for their elusive cellular targets and in the elucidation of the functional role of ras gene products.
Santos
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Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Nebreda
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D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras); D011519:Proto-Oncogenes; D013329:Structure-Activity Relationship
D006150:Guanine Nucleotides; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)