{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:52:38Z","timestamp":1789912358784,"version":"4.0.1"},"reference-count":230,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,9]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> Guanosine triphosphate (GTP)\u2014binding proteins, also known as G proteins, play important roles in the regulation of cell growth and differentiation by transmitting intracellular signals from cell surface receptors. In this paper, the authors review G protein signaling in general and its aberrations in four human nervous system tumors.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> In the nervous system, four tumor types have been associated with aberrant G protein signaling. The first tumor type includes astrocytomas, which have increased levels of the activated form of the small G protein, p21-ras, without primary oncogenic p21-ras mutations. The likely source for increased p21-ras activity in sporadically occurring astrocytomas is overexpressed or constitutively activated growth factor receptors, whereas in neurofibromatosis Type 1 (NF1)\u2014associated astrocytomas, the source is a loss of expression of neurofibromin, a major inactivator of p21-ras (ras\u2014GTPase activating protein [GAP]). The second type of tumor associated with aberrant G protein signaling includes sporadic and NF1-associated neurofibromas and malignant peripheral nerve sheath tumors, which also have increased p21-ras activity due to a loss of neurofibromin expression. The third tumor type includes subependymal giant cell astrocytomas as part of the tuberous sclerosis complex (TSC). These tumors display a loss of tuberin expression due to germline mutations in the <jats:italic>TSC2<\/jats:italic> gene. Tuberin functions as an inactivator of the small G protein rap1B (rap1-GAP) and, hence, loss of its expression could lead to increased rap1B activity. In addition to TSC-associated tumors, the authors demonstrate that the majority of sporadically occurring astrocytomas display either loss of tuberin or overexpression of rap1B. This suggests that increased rap1B activity, which can augment p21-ras\u2014mediated signals, also contributes to G protein\u2014mediated aberrant signaling in sporadically occurring astrocytomas. The fourth tumor type includes a significant subset of pituitary adenomas that show constitutive activation of the G\u03b1 subunit of the large heterotrimeric Gs protein, which is involved in hormone receptor signaling. The net result of this aberrant activation is increased cyclic adenosine monophosphate and mitogenic tumor-promoting signals.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> The authors' review of G protein signaling and aberrations in this process is made with the long-term view that increased understanding of relevant signaling pathways will eventually lead to novel biological targeted therapies against these tumors.<\/jats:p>","DOI":"10.3171\/jns.2002.97.3.0627","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:44:05Z","timestamp":1242236645000},"page":"627-642","source":"Crossref","is-referenced-by-count":24,"title":["Aberrant G protein signaling in nervous system tumors"],"prefix":"10.3171","volume":"97","author":[{"given":"Stacey A.","family":"Woods","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Marmor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Feldkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NELSON","family":"LAU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Apicelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry","family":"Boss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Gutmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Guha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Oncogene","first-page":"323","article-title":"Induction of smg p21\/rap1A p21\/krev-1 p21 gene expression during phorbol ester-induced differentiation of a human megakaryocytic leukemia cell line.","volume":"7","author":"Adachi","year":"1992"},{"key":"b2","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1097\/00006123-199308000-00003","article-title":"Clinical and biochemical characteristics of acromegalic patients harboring gsppositive and gsp-negative pituitary tumors.","volume":"33","author":"Adams","year":"1993"},{"key":"b3","series-title":"J Clin Invest","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1172\/JCI114705","article-title":"Clinically nonfunctioning pituitary tumors are monoclonal in origin.","volume":"86","author":"Alexander","year":"1990"},{"key":"b4","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"7475","DOI":"10.1073\/pnas.95.13.7475","article-title":"Mitogenic and oncogenic properties of the small G protein Rap1b.","volume":"95","author":"Altschuler","year":"1998"},{"key":"b5","series-title":"Mol Cell Biol","first-page":"487","article-title":"A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity.","volume":"13","author":"Andersen","year":"1993"},{"key":"b6","series-title":"Nat Genet","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/ng0293-118","article-title":"Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines.","volume":"3","author":"Andersen","year":"1993"},{"key":"b7","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/hmg\/5.4.503","article-title":"Site and sequence specific DNA methylation in the neurofibromatosis (NF1) gene includes C5839T: the site of the recurrent substitution mutation in exon 31.","volume":"5","author":"Andrews","year":"1996"},{"key":"b8","series-title":"Mayo Clin Proc","first-page":"641","article-title":"Pituitary adenoma in Olmstead county, Minnesota, 1937\u20131977. A report of an increasing incidence of diagnosis in women of childbearing age.","volume":"53","author":"Annegers","year":"1978"},{"key":"b9","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1093\/hmg\/9.2.237","article-title":"Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1.","volume":"9","author":"Ars","year":"2000"},{"key":"b10","series-title":"J Clin Endocrinol Metab","first-page":"4386","article-title":"Activating mutations of the Gs alpha gene are associated with low levels of Gs alpha protein in growth hormone-secreting tumors.","volume":"83","author":"Ballare","year":"1998"},{"key":"b11","series-title":"Cell","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/0092-8674(90)90151-4","article-title":"The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.","volume":"63","author":"Ballester","year":"1990"},{"key":"b12","series-title":"Annu Rev Biochem","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1146\/annurev.bi.56.070187.004023","article-title":"ras genes.","volume":"56","author":"Barbacid","year":"1987"},{"key":"b13","series-title":"J Clin Endocrinol Metab","first-page":"1604","article-title":"Prognostic and therapeutic consequences of Gs alpha mutations in somatotroph adenomas.","volume":"83","author":"Barlier","year":"1998"},{"key":"b14","series-title":"J Clin Endocrinol Metab","first-page":"2759","article-title":"Impact of gsp oncogene on the expression of genes coding for Gsalpha, Pit-1, Gi2alpha, and somatostatin receptor 2 in human somatotroph adenomas: involvement in octreotide sensitivity.","volume":"84","author":"Barlier","year":"1999"},{"key":"b15","series-title":"Nature","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/356713a0","article-title":"Aberrant regulation of ras proteins in malignant tumor cells from type 1 neurofibromatosis patients.","volume":"356","author":"Basu","year":"1992"},{"key":"b16","series-title":"DNA Cell Biol","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1089\/dna.1992.11.727","article-title":"Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line.","volume":"11","author":"Bernards","year":"1992"},{"key":"b17","series-title":"Cell","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/S0092-8674(05)80056-X","article-title":"Receptor-to-effector signaling through G proteins: roles for beta gamma dimers as well as alpha subunits.","volume":"71","author":"Birnbaumer","year":"1992"},{"key":"b18","series-title":"Biochim Biophys Acta","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/0304-4157(90)90007-Y","article-title":"Receptor-effector coupling by G proteins.","volume":"1031","author":"Birnbaumer","year":"1990"},{"key":"b19","series-title":"Biochem J","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3220001","article-title":"Regulatory mechanisms that modulate signalling by G-protein-coupled receptors.","volume":"322","author":"Bohm","year":"1997"},{"key":"b20","series-title":"Embo J","doi-asserted-by":"publisher","first-page":"6776","DOI":"10.1093\/emboj\/17.23.6776","article-title":"All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral.","volume":"17","author":"Bos","year":"1998"},{"key":"b21","series-title":"Cancer Res","first-page":"4682","article-title":"ras oncogenes in human cancer: a review.","volume":"49","author":"Bos","year":"1989"},{"key":"b22","series-title":"Genes Dev","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1101\/gad.8.9.1019","article-title":"Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues.","volume":"8","author":"Brannan","year":"1994"},{"key":"b23","series-title":"J Cell Sci","doi-asserted-by":"publisher","first-page":"3011","DOI":"10.1242\/jcs.110.24.3011","article-title":"Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures.","volume":"110","author":"Bretscher","year":"1997"},{"key":"b24","series-title":"Cell","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/0092-8674(92)90306-W","article-title":"The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway.","volume":"70","author":"Bucci","year":"1992"},{"key":"b25","series-title":"Cell","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/0092-8674(93)90146-H","article-title":"Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor.","volume":"73","author":"Buday","year":"1993"},{"key":"b26","series-title":"Tumors of the Central Nervous System.","author":"Burger","year":"1994"},{"key":"b27","series-title":"Nature","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/350074a0","article-title":"Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene.","volume":"350","author":"Burton","year":"1991"},{"key":"b28","series-title":"J Neuroendocrinol","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1046\/j.1365-2826.1996.04902.x","article-title":"Alteration of G alpha subunits mRNA levels in bromocriptine resistant prolactinomas.","volume":"8","author":"Caccavelli","year":"1996"},{"key":"b29","series-title":"Oncogene","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1038\/sj.onc.1202174","article-title":"Increasing complexity of Ras signaling.","volume":"17","author":"Campbell","year":"1998"},{"key":"b30","series-title":"Cell","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0092-8674(91)90639-G","article-title":"Oncogenes and signal transduction.","volume":"64","author":"Cantley","year":"1991"},{"key":"b31","series-title":"Genes Chromosomes Cancer","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1002\/(SICI)1098-2264(199601)15:1<18::AID-GCC3>3.0.CO;2-7","article-title":"Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas.","volume":"15","author":"Carbonara","year":"1996"},{"key":"b32","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1093\/hmg\/3.10.1829","article-title":"9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene.","volume":"3","author":"Carbonara","year":"1994"},{"key":"b33","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"3307","DOI":"10.1073\/pnas.74.8.3307","article-title":"Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site.","volume":"74","author":"Cassel","year":"1977"},{"key":"b34","series-title":"Brain Tumor Statistics: 1990\u20131994. 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Role of B-raf.","volume":"274","author":"Dugan","year":"1999"},{"key":"b56","series-title":"Nature","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/363045a0","article-title":"Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation.","volume":"363","author":"Egan","year":"1993"},{"key":"b57","series-title":"Am J Hum Genet","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1086\/302747","article-title":"Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1.","volume":"66","author":"Eisenbarth","year":"2000"},{"key":"b58","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"18871","DOI":"10.1074\/jbc.M011514200","article-title":"Dual growth arrest pathways in astrocytes and astrocytic tumors in response to Raf-1 activation.","volume":"276","author":"Fanton","year":"2001"},{"key":"b59","series-title":"Nature","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/376524a0","article-title":"Calcium activation of Ras mediated by neuronal exchange factor Ras-GRF.","volume":"376","author":"Farnsworth","year":"1995"},{"key":"b60","series-title":"Surg Neurol","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/S0090-3019(97)00356-X","article-title":"Neurofibromatosis type 1 peripheral nerve tumors: aberrant activation of the Ras pathway.","volume":"51","author":"Feldkamp","year":"1999"},{"key":"b61","series-title":"Can J Neurol Sci","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1017\/S0317167100033990","article-title":"Neurofibromatosis type 1: piecing the puzzle together.","volume":"25","author":"Feldkamp","year":"1998"},{"key":"b62","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1097\/00006123-199912000-00034","article-title":"Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens.","volume":"45","author":"Feldkamp","year":"1999"},{"key":"b63","series-title":"Ann NY Acad Sci","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1749-6632.1999.tb09430.x","article-title":"The farnesyltransferase inhibitor L-744, 832 inhibits the growth of astrocytomas through a combination of antiproliferative, antiangiogenic, and proapoptotic activities.","volume":"886","author":"Feldkamp","year":"1999"},{"key":"b64","series-title":"Int J Cancer","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1002\/(SICI)1097-0215(19990331)81:1<118::AID-IJC20>3.0.CO;2-5","article-title":"Normoxic and hypoxic regulation of vascular endothelial growth factor (VEGF) by astrocytoma cells is mediated by Ras.","volume":"81","author":"Feldkamp","year":"1999"},{"key":"b65","series-title":"Cancer Res","first-page":"4425","article-title":"Isotype-specific Ras. 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