{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:49:45Z","timestamp":1780076985895,"version":"3.54.0"},"reference-count":28,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5228","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1995,9]]},"abstract":"<jats:p>\n            Members of the Rho family of small guanosine triphosphatases (GTPases) regulate the organization of the actin cytoskeleton; Rho controls the assembly of actin stress fibers and focal adhesion complexes, Rac regulates actin filament accumulation at the plasma membrane to produce lamellipodia and membrane ruffles, and Cdc42 stimulates the formation of filopodia. When microinjected into quiescent fibroblasts, Rho, Rac, and Cdc42 stimulated cell cycle progression through G1 and subsequent DNA synthesis. Furthermore, microinjection of dominant negative forms of Rac and Cdc42 or of the Rho inhibitor C3 transferase blocked serum-induced DNA synthesis. Unlike Ras, none of the Rho GTPases activated the mitogen-activated protein kinase (MAPK) cascade that contains the protein kinases c-Raf1, MEK (MAPK or ERK kinase), and ERK (extracellular signal-regulated kinase). Instead, Rac and Cdc42, but not Rho, stimulated a distinct MAP kinase, the c-Jun kinase JNK\/SAPK (Jun NH\n            <jats:sub>2<\/jats:sub>\n            -terminal kinase or stress-activated protein kinase). Rho, Rac, and Cdc42 control signal transduction pathways that are essential for cell growth.\n          <\/jats:p>","DOI":"10.1126\/science.7652575","type":"journal-article","created":{"date-parts":[[2006,10,27]],"date-time":"2006-10-27T18:19:42Z","timestamp":1161973182000},"page":"1270-1272","source":"Crossref","is-referenced-by-count":953,"title":["An Essential Role for Rho, Rac, and Cdc42 GTPases in Cell Cycle Progression Through G\n            <sub>1<\/sub>"],"prefix":"10.1126","volume":"269","author":[{"given":"Michael F.","family":"Olson","sequence":"first","affiliation":[{"name":"CRC Signal Transduction and Oncogene Group, Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1 E 6BT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Ashworth","sequence":"additional","affiliation":[{"name":"Chester Beatty Laboratories, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Hall","sequence":"additional","affiliation":[{"name":"CRC Signal Transduction and Oncogene Group, Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1 E 6BT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/351122a0","volume":"351","year":"1991","unstructured":"BINETRUY, B, HA-RAS AUGMENTS C-JUN ACTIVITY AND STIMULATES PHOSPHORYLATION OF ITS ACTIVATION DOMAIN, NATURE 351: 122 (1991).","journal-title":"NATURE"},{"key":"e_1_2_1_2_1","first-page":"3610","volume":"5","year":"1985","unstructured":"EVAN, G.I., ISOLATION OF MONOCLONAL-ANTIBODIES SPECIFIC FOR HUMAN C-MYC PROTO-ONCOGENE PRODUCT, MOLECULAR AND CELLULAR BIOLOGY 5: 3610 (1985).","journal-title":"MOLECULAR AND CELLULAR BIOLOGY"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1101\/gad.7.11.2135","volume":"7","year":"1993","unstructured":"HIBI, M, IDENTIFICATION OF AN ONCOPROTEIN-RESPONSIVE AND UV-RESPONSIVE PROTEIN-KINASE THAT BINDS AND POTENTIATES THE C-JUN ACTIVATION DOMAIN, GENES & DEVELOPMENT 7: 2135 (1993).","journal-title":"GENES & DEVELOPMENT"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90361-F"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8385802"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1002\/j.1460-2075.1992.tb05587.x","volume":"11","year":"1992","unstructured":"LEBERER, E, THE PROTEIN-KINASE HOMOLOG STE20P IS REQUIRED TO LINK THE YEAST PHEROMONE RESPONSE G-PROTEIN BETA-GAMMA SUBUNITS TO DOWNSTREAM SIGNALING COMPONENTS, EMBO JOURNAL 11: 4815 (1992).","journal-title":"EMBO JOURNAL"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/369411a0","volume":"369","year":"1994","unstructured":"LEEVERS, S.J., REQUIREMENT FOR RAS IN RAF ACTIVATION IS OVERCOME BY TARGETING RAF TO THE PLASMA-MEMBRANE, NATURE 369: 411 (1994).","journal-title":"NATURE"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716521"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/367040a0"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90401-8"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/0959-437X(94)90095-7","volume":"4","year":"1994","unstructured":"MARSHALL, C.J., CURR OPIN GENE DEV 4: 82 (1994).","journal-title":"CURR OPIN GENE DEV"},{"key":"e_1_2_1_12_1","first-page":"6683","volume":"14","year":"1994","unstructured":"MINDEN, A, C-JUN N-TERMINAL PHOSPHORYLATION CORRELATES WITH ACTIVATION OF THE JNK SUBGROUP BUT NOT THE ERK SUBGROUP OF MITOGEN-ACTIVATED PROTEIN-KINASES, MOLECULAR AND CELLULAR BIOLOGY 14: 6683 (1994).","journal-title":"MOLECULAR AND CELLULAR BIOLOGY"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7992057"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/313241a0","volume":"313","year":"1985","unstructured":"MULCAHY, L.S., REQUIREMENT FOR RAS PROTO-ONCOGENE FUNCTION DURING SERUM-STIMULATED GROWTH OF NIH-3T3-CELLS, NATURE 313: 241 (1985).","journal-title":"NATURE"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0006-291X(90)91760-P","volume":"167","year":"1990","unstructured":"NISHIKI, T, ADP-RIBOSYLATION OF THE RHO\/RAC PROTEINS INDUCES GROWTH-INHIBITION, NEURITE OUTGROWTH AND ACETYLCHOLINE ESTERASE IN CULTURED PC-12 CELLS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 167: 265 (1990).","journal-title":"BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90370-4"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/374457a0","volume":"374","year":"1995","unstructured":"QLU, R.G., NATURE 374: 457 (1995).","journal-title":"NATURE"},{"key":"e_1_2_1_18_1","first-page":"452","volume":"90","year":"1993","unstructured":"RAMER, S.W., A DOMINANT TRUNCATION ALLELE IDENTIFIES A GENE, STE20, THAT ENCODES A PUTATIVE PROTEIN-KINASE NECESSARY FOR MATING IN SACCHAROMYCES-CEREVISIAE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 452 (1993).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90163-7"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90164-8"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1101\/gad.8.24.2974","volume":"8","year":"1994","unstructured":"ROBERTS, R.L., ELEMENTS OF A SINGLE MAP KINASE CASCADE IN SACCHAROMYCES-CEREVISIAE MEDIATE 2 DEVELOPMENTAL PROGRAMS IN THE SAME CELL-TYPE - MATING AND INVASIVE GROWTH, GENES & DEVELOPMENT 8: 2974 (1994).","journal-title":"GENES & DEVELOPMENT"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/372794a0"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"20232","DOI":"10.1016\/S0021-9258(20)80719-4","volume":"268","year":"1993","unstructured":"SCHAAP, D, A DOMINANT-NEGATIVE MUTANT OF RAF BLOCKS MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION BY GROWTH-FACTORS AND ONCOGENIC P21(RAS), JOURNAL OF BIOLOGICAL CHEMISTRY 268: 20232 (1993).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_24_1","first-page":"3507","volume":"12","year":"1992","unstructured":"SMEAL, T, ONCOPROTEIN-MEDIATED SIGNALING CASCADE STIMULATES C-JUN ACTIVITY BY PHOSPHORYLATION OF SERINE-63 AND SERINE-73, MOLECULAR AND CELLULAR BIOLOGY 12: 3507 (1992).","journal-title":"MOLECULAR AND CELLULAR BIOLOGY"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/354494a0"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7811320"},{"key":"e_1_2_1_27_1","first-page":"1449","volume":"8","year":"1993","unstructured":"YAMAMOTO, M, ADP-RIBOSYLATION OF THE RHOA GENE-PRODUCT BY BOTULINUM C3 EXOENZYME CAUSES SWISS 3T3 CELLS TO ACCUMULATE IN THE G(1) PHASE OF THE CELL-CYCLE, ONCOGENE 8: 1449 (1993).","journal-title":"ONCOGENE"},{"key":"e_1_2_1_28_1","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/372798a0","volume":"372","year":"1994","unstructured":"YAN, M.H., ACTIVATION OF STRESS-ACTIVATED PROTEIN-KINASE BY MEKK1 PHOSPHORYLATION OF ITS ACTIVATOR SEK1, NATURE 372: 798 (1994).","journal-title":"NATURE"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.7652575","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:54:06Z","timestamp":1705294446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.7652575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,9]]},"references-count":28,"journal-issue":{"issue":"5228","published-print":{"date-parts":[[1995,9]]}},"alternative-id":["10.1126\/science.7652575"],"URL":"https:\/\/doi.org\/10.1126\/science.7652575","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,9]]}}}