ArticleMolecular and cellular biology2003
p27Kip1 inhibition of GRB2-SOS formation can regulate Ras activation.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Article
- A survey and evaluations of histogram-based statistics in alignment-free sequence comparison.Briefings in bioinformatics · 2019Article
- MEN4 andEndocrine-related cancer · 2017Review
- Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma.Blood · 2017Article
- The cyclin-like protein, SPY1, regulates the ERα and ERK1/2 pathways promoting tamoxifen resistance.Oncotarget · 2017Article
- p27kip1 expression limits H-Ras-driven transformation and tumorigenesis by both canonical and non-canonical mechanisms.Oncotarget · 2016Article
- The non-canonical functions of p27(Kip1) in normal and tumor biology.Cell cycle (Georgetown, Tex.) · 2016Review
- Meet me in the cytoplasm: A role for p27(Kip1) in the control of H-Ras.Small GTPases · 2016Review
- Article
- Allostery mediates ligand binding to Grb2 adaptor in a mutually exclusive manner.Journal of molecular recognition : JMR · 2013Article
- Analysis of activated platelet-derived growth factor β receptor and Ras-MAP kinase pathway in equine sarcoid fibroblasts.BioMed research international · 2013Article
- Tyrosine phosphorylation of the p21 cyclin-dependent kinase inhibitor facilitates the development of proneural glioma.The Journal of biological chemistry · 2012Article
- Bivalent binding drives the formation of the Grb2-Gab1 signaling complex in a noncooperative manner.The FEBS journal · 2012Article
- Loss of protein-tyrosine phosphatase α (PTPα) increases proliferation and delays maturation of oligodendrocyte progenitor cells.The Journal of biological chemistry · 2012Article
- Multivalent binding and facilitated diffusion account for the formation of the Grb2-Sos1 signaling complex in a cooperative manner.Biochemistry · 2012Article
- A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization.Human mutation · 2010Article
- p27 suppresses arsenite-induced Hsp27/Hsp70 expression through inhibiting JNK2/c-Jun- and HSF-1-dependent pathways.The Journal of biological chemistry · 2010Article
- Article
- Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control.Archives of biochemistry and biophysics · 2010Article
- SH3 domains of Grb2 adaptor bind to PXpsiPXR motifs within the Sos1 nucleotide exchange factor in a discriminate manner.Biochemistry · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
p27(Kip1) (p27) is often inappropriately downregulated in aggressive human cancers. Although p27 can inhibit cyclin-dependent kinases (CDKs), low p27 does not always correlate with increased CDK activity. Furthermore, cells derived from p27(-/-) mice respond to antimitogens, maintain restriction point control, and do not deregulate CDKs. Thus, disruption of a p27 function other than CDK inhibition may contribute to the disease state. A yeast two-hybrid screen identified growth factor receptor-bound protein 2 (GRB2) as a p27 binding partner. We now demonstrate that p27 can inhibit GRB2 function by blocking its association with the guanine nucleotide exchange factor SOS. Endogenous p27 is rapidly exported from the nucleus to the cytoplasm in response to mitogen stimulation, where it binds GRB2 concomitant with a decrease in GRB2-associated SOS. As predicted, mitogen-stimulated p27(-/-) cells maintained their GRB2-SOS complexes for significantly longer. The Ras/mitogen-activated protein kinase pathway does not appear to be deregulated in cells lacking p27 despite excess GRB2-SOS, suggesting that additional control mechanisms are present. A transient-transfection approach was employed to show that p27 can inhibit Ras activation by targeting GRB2 and further revealed that the CDK and GRB2 inhibitory functions of p27 are separable and distinct. Thus, p27 downregulation may compromise control of Ras, one of the most common oncogenic events in human cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.