Rap1 is a small G protein belonging to the RAS superfamily. Rap1 signalling has effects on cell growth, cell proliferation and involves in regulation of the mitogen activated protein (MAP) kinase or ERK (extracellular signal regulated kinase) cascade. Rap1 will directly activate ERK through B-Raf. B-Raf is a member of Raf family, and presents in neuronal and hematopoietic cells. Oncogenic mutations of gene RAS are most frequent and detected in 20% - 30% of human leukemias and 10% - 15% of MDS cases. The review summarizes the regulatory function of Rap1 in development of hematopoietic cells and effect of Rap1 in hematologic malignancies.
Hematologic Neoplasms ; genetics ; metabolism ; Humans ; Signal Transduction ; rap1 GTP-Binding Proteins ; genetics ; metabolism

OBJECTIVETo study the differential gene expression profiles between the normal and aspermia human testes by genechips.

METHODSProbes were prepared from mRNA extracted from both normal and aspermia testes and employed on Biostar H-40s genechips to detect the differential gene expression profiles. A distinctly up-regulated gene RAP1A was analyzed by bibliogrphic retrieval.

RESULTSSix hundred and twenty-three differential expressed genes were found, among which the distinctly up-regulated gene RAP1A was closely related to human sperm regulation.

CONCLUSIONSScreening the differential gene expression profiles between the normal and aspermia human testes by genechips can be used in the study of aspermia-related genes.

Adult ; Gene Expression Profiling ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Oligospermia ; genetics ; rap1 GTP-Binding Proteins ; genetics

OBJECTIVETo explore the hematopoietic pathophysiology of myelodysplastic syndrome (MDS) at stem/progenitor cell level by analyzing the gene expression profiles associated with hematopoiesis.

METHODSThe differentially expressed genes which were involved in the hematopoiesis were screened by microarray using CD34(+) cells from MDS patients firstly. RQ-PCR was then applied to validate the screened genes using CD34(+) cells from MDS-RA patients who had normal karyotype. The linkages with hematopoiesis among these validated genes were analyzed.

RESULTSAmong the differentially expressed genes in CD34(+) cells of MDS-RA patients, Rap1GAP was up-regulated significantly (P < 0.01). Cadherins, which can interplay with Rap1, including N-cadherin and E-cadherin, were down-regulated significantly (P < 0.01). β-catenin, a downstream effector of cadherins, was highly expressed in MDS-RA patients (P < 0.01). c-myc binding protein was down-regulated (P < 0.01), and c-myc promoter binding protein was up-regulated (P < 0.01). Rac1, Rac2 and Cdc42, which belong to RhoGTPases family and are associated with the cell morphology and hematopoiesis, were all expressed highly in MDS-RA patients (P < 0.01).

CONCLUSIONThe abnormal expression of cadherin, β-catenin and c-myc associated genes were closely related to the dysplastic hematopoiesis of MDS. The down regulation of cadherin was associated with the positive feedback mechanism between Rap1 and cadherin. The aberrant expression of Rac1, Rac2 and Cdc42 may contribute to the morphological dysplasia of MDS.

Cadherins ; genetics ; metabolism ; Gene Expression ; Gene Expression Profiling ; Genes, myc ; Humans ; Myelodysplastic Syndromes ; genetics ; metabolism ; beta Catenin ; genetics ; rap1 GTP-Binding Proteins ; genetics ; metabolism

AIMTo evaluate the Rap1A mRNA expression and its significance in the testes of normal and azoospermic subjects.

METHODSA cDNA microarray that contained Rap1A and some other genes such as RBM, EIF1AY was used to identify the differential gene expression profiles between the normal and azoospermic testes. cDNA probes were prepared by labeling mRNA from azoospermic and normal testicular tissues through reverse transcription with Cy5-dUTP and Cy3-dUTP, respectively. The mixed cDNA probes were then hybridized with cDNA microarray (each containing 4096 unique human cDNA sequences). The fluorescent signals were scanned and the values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated. In situ hybridization was employed to detect the expression of Rap1A in the testes of 10 fertile and 39 azoospermic subjects.

RESULTSOne hundred and twenty-eight differentially expressed genes were found to be possibly related to azoospermia, of which 56 were up-regulated and 72, down-regulated genes. The mRNA expression of Rap1A in the spermatogenic cells of azoospermic was stronger than that in those of the fertile testes.

CONCLUSIONRap1A may play certain roles in the development of azoospermia.

Adult ; Gene Expression ; Humans ; In Situ Hybridization ; Male ; Oligospermia ; metabolism ; RNA, Messenger ; analysis ; Spermatozoa ; chemistry ; Testis ; chemistry ; rap1 GTP-Binding Proteins ; genetics ; physiology

Rap1A is a small G protein implicated in a spectrum of biological processes such as cell proliferation, adhesion, differentiation, and embryogenesis. The downstream effectors through which Rap1A mediates its diverse effects are largely unknown. Here we show that Rap1A, but not the related small G proteins Rap2 or Ras, binds the tumor suppressor Ras association domain family 1A (RASSF1A) in a manner that is regulated by phosphorylation of RASSF1A. Interaction with Rap1A is shown to influence the effect of RASSF1A on microtubule behavior.
Amino Acid Sequence ; Animals ; COS Cells ; Cercopithecus aethiops ; HEK293 Cells ; Humans ; Intracellular Space ; metabolism ; Microtubules ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Phosphorylation ; Protein Binding ; Protein Structure, Secondary ; Substrate Specificity ; Tumor Suppressor Proteins ; chemistry ; metabolism ; rap1 GTP-Binding Proteins ; metabolism

This study was aimed to investigate the expression levels of TRF1, TRF2 and RAP1 mRNA in peripheral blood mononuclear cells of patients with acquired aplastic anemia, and to explore their relation with onset of acquired aplastic anemia. Peripheral blood mononuclear cells of 40 patients with acquired aplastic anemia and 20 normal subjects as control were collected to detect mRNA expression of TRF1, TRF2 and RAP1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of TRF1 and RAP1 in peripheral blood mononuclear cells of patients with acquired aplastic anemia were significantly higher than that in normal controls (P < 0.05), while the expression level of TRF2 was lower than that in normal controls (P < 0.01). There was significant correlation between TRF2 and RAP1 expressions level (r = 0.522, P = 0.001). It is concluded that the changes in expression levels of TRF1, TRF2 and RAP1 may play a role in the pathogenesis of acquired aplastic anemia.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic ; blood ; Case-Control Studies ; Child ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Telomeric Repeat Binding Protein 1 ; metabolism ; Telomeric Repeat Binding Protein 2 ; metabolism ; Young Adult ; rap1 GTP-Binding Proteins ; metabolism