{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRAP1A is a pivotal small GTPase that orchestrates cell–cell and cell–matrix adhesion by regulating the assembly and stabilization of junctional complexes. In epithelial and endothelial cells, RAP1A is activated downstream of cAMP and its effector Epac, which enhances adherens junction formation through E‐cadherin recruitment and strengthens VE‐cadherin–mediated contacts, thereby reducing paracellular permeability and modulating leukocyte transmigration. In these contexts, RAP1A also participates in relaying signals from cell adhesion molecules such as JAM‐A that regulate β1 integrin expression and cellular morphology. Collectively, these studies underscore that RAP1A plays a central role in modulating intercellular adhesion and barrier function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its junction‐stabilizing functions, RAP1A localizes dynamically to the plasma membrane where it steers integrin activation and cell spreading. Through interactions with effector proteins such as RIAM and talin, RAP1A mediates integrin affinity changes that are essential for cytoskeletal rearrangements, lamellipodia extension, and directed cell migration. This role is also observed in other cell types, including neurons where RAP1A activation contributes to neurite outgrowth, and in platelets where it modulates adhesion in response to Eph/ephrin signals. These findings demonstrate that RAP1A functions as a key regulator of intracellular signals leading to controlled cell migration and adhesion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in adhesion and migration, emerging evidence links RAP1A to diverse pathophysiological processes including tumorigenesis, angiogenesis, and chemotherapeutic responsiveness. Genetic studies have associated RAP1A variants with osteoporosis‐related traits, while altered RAP1A signaling—in part via its nuclear translocation—has been implicated in squamous cell carcinoma and ovarian cancer metastasis. Furthermore, aberrant modulation of RAP1A, whether by changes in upstream GPCR signaling or by deregulation through miRNAs and scaffolding proteins such as SHANKs, contributes to altered integrin activation and cell cycle progression in cancer cells. In aggregate, these findings indicate that precise spatiotemporal control of RAP1A activity is critical for maintaining normal cell behavior, and its dysregulation may serve as both a biomarker and a therapeutic target in various diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Catherine Hogan, Norberto Serpente, Patricia Cogram, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rap1 regulates the formation of E-cadherin-based cell-cell contacts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.15.6690-6700.2004"}], "href": "https://doi.org/10.1128/MCB.24.15.6690-6700.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15254236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15254236"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xavier Cullere, Sunil K Shaw, Lorna Andersson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-05-1987"}], "href": "https://doi.org/10.1182/blood-2004-05-1987"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15374886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15374886"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shigetomo Fukuhara, Atsuko Sakurai, Hideto Sano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclic AMP potentiates vascular endothelial cadherin-mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.1.136-146.2005"}], "href": "https://doi.org/10.1128/MCB.25.1.136-146.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15601837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15601837"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Erika S Wittchen, Rebecca A Worthylake, Patrick Kelly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M412595200"}], "href": "https://doi.org/10.1074/jbc.M412595200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15661741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15661741"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kenneth J Mandell, Brian A Babbin, Asma Nusrat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on beta1 integrins and Rap1 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M412650200"}], "href": "https://doi.org/10.1074/jbc.M412650200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15677455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15677455"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Fiorella Balzac, Maria Avolio, Simona Degani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02584"}], "href": "https://doi.org/10.1242/jcs.02584"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16219685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16219685"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Seema Sehrawat, Xavier Cullere, Sunita Patel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Epac1, an exchange factor for Rap GTPases, in endothelial microtubule dynamics and barrier function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e06-10-0972"}], "href": "https://doi.org/10.1091/mbc.e06-10-0972"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18172027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18172027"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Eric A Severson, Winston Y Lee, Christopher T Capaldo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e08-10-1014"}], "href": "https://doi.org/10.1091/mbc.e08-10-1014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19176753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19176753"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Trever G Bivona, Heidi H Wiener, Ian M Ahearn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200311093"}], "href": "https://doi.org/10.1083/jcb.200311093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14757755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14757755"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "William T Arthur, Lawrence A Quilliam, Jonathan A Cooper "}, {"type": "b", "children": [{"type": "t", "text": "Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200404068"}], "href": "https://doi.org/10.1083/jcb.200404068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15479739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15479739"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jorrit M Enserink, Leo S Price, Trond Methi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M404599200"}], "href": "https://doi.org/10.1074/jbc.M404599200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15302884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15302884"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "J Dedrick Jordan, John Cijiang He, Narat J Eungdamrong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cannabinoid receptor-induced neurite outgrowth is mediated by Rap1 activation through G(alpha)o/i-triggered proteasomal degradation of Rap1GAPII."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M411521200"}], "href": "https://doi.org/10.1074/jbc.M411521200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15657046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15657046"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Meghan M Murphy, Mohamed A Zayed, Allyson Evans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-07-2881"}], "href": "https://doi.org/10.1182/blood-2004-07-2881"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15613546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15613546"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Oliver Danielewski, Jan Schultess, Albert Smolenski "}, {"type": "b", "children": [{"type": "t", "text": "The NO/cGMP pathway inhibits Rap 1 activation in human platelets via cGMP-dependent protein kinase I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH04-09-0582"}], "href": "https://doi.org/10.1160/TH04-09-0582"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15711749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15711749"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Guillaume Carmona, Stephan Göttig, Alessia Orlandi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-02-138438"}], "href": "https://doi.org/10.1182/blood-2008-02-138438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18805968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18805968"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jeffrey C Nolz, Lucas P Nacusi, Colin M Segovis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200801121"}], "href": "https://doi.org/10.1083/jcb.200801121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18809728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18809728"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Tatsuo Kinashi, Memet Aker, Maya Sokolovsky-Eisenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-07-2499"}], "href": "https://doi.org/10.1182/blood-2003-07-2499"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14551137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14551137"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Nicolas Prévost, Donna S Woulfe, Massimiliano Tognolini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signaling by ephrinB1 and Eph kinases in platelets promotes Rap1 activation, platelet adhesion, and aggregation via effector pathways that do not require phosphorylation of ephrinB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-06-1781"}], "href": "https://doi.org/10.1182/blood-2003-06-1781"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14576067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14576067"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Masakazu Hattori, Nagahiro Minato "}, {"type": "b", "children": [{"type": "t", "text": "Rap1 GTPase: functions, regulation, and malignancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvg180"}], "href": "https://doi.org/10.1093/jb/mvg180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14607972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14607972"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Yi-Hsiang Hsu, M Carola Zillikens, Scott G Wilson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000977"}], "href": "https://doi.org/10.1371/journal.pgen.1000977"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20548944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20548944"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Liqin Du, Maria C Subauste, Christopher DeSevo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0039167"}], "href": "https://doi.org/10.1371/journal.pone.0039167"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22723956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22723956"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Mistre Alemayehu, Magdalena Dragan, Cynthia Pape, et al. "}, {"type": "b", "children": [{"type": "t", "text": "β-Arrestin2 regulates lysophosphatidic acid-induced human breast tumor cell migration and invasion via Rap1 and IQGAP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0056174"}], "href": "https://doi.org/10.1371/journal.pone.0056174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23405264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23405264"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Maho Takahashi, Tara J Dillon, Chang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase A-dependent phosphorylation of Rap1 regulates its membrane localization and cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.466904"}], "href": "https://doi.org/10.1074/jbc.M113.466904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23946483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23946483"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "A Post, W J Pannekoek, B Ponsioen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rap1 Spatially Controls ArhGAP29 To Inhibit Rho Signaling during Endothelial Barrier Regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01453-14"}], "href": "https://doi.org/10.1128/MCB.01453-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25963656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25963656"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Nina Bögershausen, I-Chun Tsai, Esther Pohl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI80102"}], "href": "https://doi.org/10.1172/JCI80102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26280580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26280580"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "María Luisa Lozano, Aaron Cook, José María Bastida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2015-11-683102"}], "href": "https://doi.org/10.1182/blood-2015-11-683102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27235135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27235135"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Lili Lu, Jingshu Wang, Yougen Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rap1A promotes ovarian cancer metastasis via activation of ERK/p38 and notch signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.946"}], "href": "https://doi.org/10.1002/cam4.946"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27925454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27925454"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Johanna Lilja, Thomas Zacharchenko, Maria Georgiadou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3487"}], "href": "https://doi.org/10.1038/ncb3487"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28263956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28263956"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Markus Klinger, Oliver Kudlacek, Markus G Seidel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAP kinase stimulation by cAMP does not require RAP1 but SRC family kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200556200"}], "href": "https://doi.org/10.1074/jbc.M200556200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12082090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12082090"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "John M Schmitt, Philip J S Stork "}, {"type": "b", "children": [{"type": "t", "text": "Galpha and Gbeta gamma require distinct Src-dependent pathways to activate Rap1 and Ras."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M204006200"}], "href": "https://doi.org/10.1074/jbc.M204006200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12221082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12221082"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Raj S Mitra, Zhaocheng Zhang, Bradley S Henson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rap1A and rap1B ras-family proteins are prominently expressed in the nucleus of squamous carcinomas: nuclear translocation of GTP-bound active form."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1206534"}], "href": "https://doi.org/10.1038/sj.onc.1206534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "13679863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/13679863"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Tone Bryn, Milada Mahic, Jorrit M Enserink, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cyclic AMP-Epac1-Rap1 pathway is dissociated from regulation of effector functions in monocytes but acquires immunoregulatory function in mature macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.176.12.7361"}], "href": "https://doi.org/10.4049/jimmunol.176.12.7361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16751380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16751380"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Ha-Won Jeong, Zhigang Li, Matthew D Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IQGAP1 binds Rap1 and modulates its activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M700487200"}], "href": "https://doi.org/10.1074/jbc.M700487200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17517894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17517894"}]}]}]}