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HPMR

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RAP2A, member of RAS oncogene family OKDB#: 5539
 Symbols: RAP2A Species: human
 Synonyms: KREV, RAP2, K-REV, RbBP-30  Locus: 13q32.1 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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R-L INTERACTIONS   MGI

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General Comment Upstream Hippo signaling//// RAP2 mediates mechanoresponses of the Hippo pathway. Meng Z et al. (2018) Mammalian cells are surrounded by neighbouring cells and extracellular matrix (ECM), which provide cells with structural support and mechanical cues that influence diverse biological processes1. The Hippo pathway effectors YAP (also known as YAP1) and TAZ (also known as WWTR1) are regulated by mechanical cues and mediate cellular responses to ECM stiffness2,3. Here we identified the Ras-related GTPase RAP2 as a key intracellular signal transducer that relays ECM rigidity signals to control mechanosensitive cellular activities through YAP and TAZ. RAP2 is activated by low ECM stiffness, and deletion of RAP2 blocks the regulation of YAP and TAZ by stiffness signals and promotes aberrant cell growth. Mechanistically, matrix stiffness acts through phospholipase Cγ1 (PLCγ1) to influence levels of phosphatidylinositol 4,5-bisphosphate and phosphatidic acid, which activates RAP2 through PDZGEF1 and PDZGEF2 (also known as RAPGEF2 and RAPGEF6). At low stiffness, active RAP2 binds to and stimulates MAP4K4, MAP4K6, MAP4K7 and ARHGAP29, resulting in activation of LATS1 and LATS2 and inhibition of YAP and TAZ. RAP2, YAP and TAZ have pivotal roles in mechanoregulated transcription, as deletion of YAP and TAZ abolishes the ECM stiffness-responsive transcriptome. Our findings show that RAP2 is a molecular switch in mechanotransduction, thereby defining a mechanosignalling pathway from ECM stiffness to the nucleus.//////////////////

General function
Comment
Cellular localization
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Ovarian function
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Expression regulated by FSH, LH
Comment DNA microarray
Ovarian localization Granulosa
Comment
Follicle stages
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Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
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created: Feb. 6, 2018, 1:02 p.m. by: system   email:
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last update: Aug. 29, 2018, 3:42 p.m. by: hsueh    email:



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