However, the specific mechanisms of translocation of Rap1B and Rap2B to the cytoskeleton remain unclear. The large GP vWF is synthesized by megakaryocytes and endothelial cells, and is important in thrombus formation and platelet adhesion In a previous study, Rap2B was prevented from associating with the cytoskeleton by cytochalasin D, which did not inhibit platelet aggregation Lipid rafts are dynamic membrane microdomains abundant in cholesterol and glycosphingolipids 61 , which appear to be important for human platelet activation 62 , 63 and are also implicated in signal transduction.
Furthermore, there are specific differences in the mechanisms for agonist-induced activation of Rap1B and Rap2B, particularly in their dependence on secreted ADP in human platelets Previous studies have observed that the thrombin-induced activation of Rap2B was significantly reduced when secreted ADP was neutralized The authors also revealed that the association of Rap2B to lipid rafts is promoted by palmitoylation of C and C, which are located at the C-terminal region of the protein.
These residues are required for the complete activation of Rap2B, and are induced by stimulation of human platelets Although additional studies are required to fully elucidate the biochemical and functional characterization of Rap2B in platelets, the above previous results indicate a novel biochemical property of Rap2B, and demonstrate the important role of Rap2B in regulating the activation and aggregation of blood platelets. Inositol-specific mammalian PLC enzymes are multidomain proteins whose functions are regulated by G proteins Therefore, the data provided novel insights into the signaling events and gene expression alterations associated with the growth inhibition and apoptosis of melanoma cells, which may result in the identification of novel targets for melanoma therapy Rap2B is one of the 50 novel candidate genes cloned from differential expression cDNA libraries constructed in lung cancer cells In , Liu et al 88 used the suppression subtractive hybridization method to identify differentially expressed genes in lung squamous cell carcinoma SCC.
The results revealed that the messenger RNA and protein expression levels of Rap2B in lung cancer tissues was increased, compared with normal tissues. Although the specific mechanism remains unclear, this observation implied that Rap2B may play a potential role in the development and progression of lung SCC. Similarly to other Ras proteins, Rap2B is associated with the occurrence and development of tumors 1 , Certain studies have reported an association between the function of Rap2B and the development of malignant tumors, and increasing evidence clearly confirms this association 1 , Although the mechanism of Rap2B in cancer is not clear, the function of Rap2B relies on its gene homology and protein structure Therefore, it may be hypothesized that Rap2B is involved in tumor development.
The formation of tumors results from abnormal proliferation of normal cells, which usually present as abnormal masses in the body Numerous studies have observed that the occurrence and development of cancer are complex processes that are regulated by multiple genes and factors The abnormal activation of oncogenes and inactivation of tumor suppressor genes serve as a major contribution to tumor development The open reading frame of Rap2B shares In vivo , the number and volume of Ras-induced tumor nodules is increased significantly by JNK deficiency, and the oncogenic effects of Ras are suppressed by the JNK signaling pathway Growth arrest and apoptosis of certain tumor cells is caused by inhibition of JNK 96 — Autophagy is considered a cell survival mechanism, which is activated in response to various stress signals, including high temperature, oxidative stress and accumulation of damaged organelles The pathogenesis of clinically important disorders in a variety of organ systems contribute to the dysregulation of autophagy Staphylococcus aureus is a pathogen that colonizes the lungs of patients with cystic fibrosis and causes serious infectious diseases In , Mestre and Colombo demonstrated that S.
The authors also revealed that S. Therefore, Rap2B may regulate the autophagy and survival of S. The authors described that cell adhesion and spreading, in addition to actin polymerization and integrin-mediated Pyk2 tyrosine phosphorylation, are regulated by Rap GTPases in B cells. Consequently, the present review hypothesizes that Rap2B may regulate the immune system by promoting tumorigenesis. Although certain biochemical and functional roles of Rap2B have been elucidated, additional studies are required to fully understand the functional mechanism of Rap2B and its association with tumor development.
Previous studies have suggested that targeting Rap2B may sensitize tumor cells to undergo apoptosis in response to DNA damage, since Rap2B is a conserved pactivated gene 1. However, anticancer drugs that target Rap2B remain a theory, since an improved understanding at a molecular level of exactly how Rap2B functions as a tumor promoter is required prior to the development of novel drugs targeting Rap2B. Therefore, the identification of the functions of Rap2B may result in novel avenues of research aimed to improve therapeutics and prognosis of human malignancies.
Inhibiting the expression of Rap2B may potentially be useful in cancer therapy, and has gained attention in the treatment of various types of cancer that display increased expression of Rap2B proteins This may offer novel therapeutic strategies for the treatment of human carcinoma, and may eventually lead to the development of a novel class of anticancer drugs that target Rap2B, and promote the development of sensitive biomarkers for cancer diagnosis and treatment.
Future studies on Rap2B will provide evidence and generate mechanistic hypotheses regarding the development of cancer. Identifying and understanding the functionally important Ras family of proteins may clarify the biology of cancer and lead to novel therapeutic and diagnostic opportunities for patients affected by this disease.
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Significance of Ras Signaling in Cancer and Strategies for its Control
Ryu J, Futai K, Feliu M, Weinberg R and Sheng M: Constitutively active Rap2 transgenic mice display fewer dendritic spines, reduced extracellular signal-regulated kinase signaling, enhanced long-term depression, and impaired spatial learning and fear extinction. J Neurosci. Mol Cell Biol. Biochem Genet. Cell Death Differ. Pike LJ: Lipid rafts: Heterogeneity on the high seas. J Cell Physiol. Drin G and Scarlata S: Stimulation of phospholipase Cbeta by membrane interactions, interdomain movement, and G protein binding - how many ways can you activate an enzyme?
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Mol Biol Cell. J Leukoc Biol. BMC Cancer. Zhongguo Fei Ai Za Zhi. In Chinese. Lung Cancer. Int J Epidemiol. Cold Spring Harb Perspect Biol. PLoS One. Br J Pharmacol. Genes Dev. The emerging role of autophagy in idiopathic pulmonary fibrosis. BioMed Res Int. Specifically, it is involved in the division of newly formed vesicles from the membrane of one compartment to their fusion with another compartment-- at both the cell surface or Golgi body.
Along with division of vesicles, Dynamin is also involved in the division of organelles, cytokinesis, and pathogen resistance microbial. In mammals, there are 3 different types of genes:. When a vesicle folds in so that the outer surface becomes an inner surface, dynamin will form a spiral around the vesicle's neck. The spiral will then extend and then constrict via GTP hydrolysis. This process produces a twisting motion and results in the pinching off of the vesicle from its main body.
The twisting motion is dependent on its dynamin GTPase activity.
So far, dynamin is the only right-handed helix that produces a twisting motion right-handed twisting. Translation Factor GTPases have an important role in the initiation, elongation, and the termination of protein biosynthesis. Mizuno-Yamasaki, E. Rivera-Molina, and et al. Wikimedia Foundation, Inc. From Wikibooks, open books for an open world. Category : Book:Structural Biochemistry. Namespaces Book Discussion. Views Read Edit View history. Policies and guidelines Contact us.