Role of Rho kinases in abnormal and normal hematopoiesis. 2014

Raghuveer Singh Mali, and Simryn Kapur, and Reuben Kapur
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Department of Pediatrics, Indianapolis, Indiana, USA.

OBJECTIVE Rho kinases (ROCKs) are involved in regulating a variety of physiologic functions including cytoskeletal reorganization, migration, adhesion, survival and proliferation. They do so via activating several different downstream substrates such as myosin light chain phosphatase, LIM kinase and ezrin/radixin/moesin proteins. To date, most of the conclusions with regard to the function of ROCKs have involved the use of cell line models, pharmacologic inhibitors and dominant negative approaches. Importantly, the role of ROCK in hematopoiesis or leukemogenesis in the context of whole organism remains poorly understood. RESULTS Recent studies utilizing mice deficient in the expression of ROCK1 have begun to shed some light into the physiologic role(s) of ROCK in both normal and abnormal hematopoiesis. Findings, thus far, suggest that ROCK plays an essential role in regulating growth and survival in different hematopoietic lineages via distinct mechanisms, in part, by utilizing distinct downstream substrates including maintaining the activation of tumor-suppressor genes. CONCLUSIONS In blood cells, emerging data suggest that ROCK plays an essential role in negatively regulating inflammatory and erythropoietic stress and positively regulates the growth and survival of leukemic cells.

UI MeSH Term Description Entries
D007938 Leukemia A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006) Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D004920 Erythropoiesis The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction. Erythropoieses
D006402 Hematologic Diseases Disorders of the blood and blood forming tissues. Blood Diseases,Hematological Diseases,Blood Disease,Disease, Blood,Disease, Hematologic,Disease, Hematological,Diseases, Blood,Diseases, Hematologic,Diseases, Hematological,Hematologic Disease,Hematological Disease
D006410 Hematopoiesis The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY). Hematopoiesis, Medullary,Haematopoiesis,Medullary Hematopoiesis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013312 Stress, Physiological The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions. Biotic Stress,Metabolic Stress,Physiological Stress,Abiotic Stress,Abiotic Stress Reaction,Abiotic Stress Response,Biological Stress,Metabolic Stress Response,Physiological Stress Reaction,Physiological Stress Reactivity,Physiological Stress Response,Abiotic Stress Reactions,Abiotic Stress Responses,Abiotic Stresses,Biological Stresses,Biotic Stresses,Metabolic Stress Responses,Metabolic Stresses,Physiological Stress Reactions,Physiological Stress Responses,Physiological Stresses,Reaction, Abiotic Stress,Reactions, Abiotic Stress,Response, Abiotic Stress,Response, Metabolic Stress,Stress Reaction, Physiological,Stress Response, Metabolic,Stress Response, Physiological,Stress, Abiotic,Stress, Biological,Stress, Biotic,Stress, Metabolic
D053595 Embryonic Stem Cells Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells. Stem Cells, Embryonic,Cell, Embryonic Stem,Cells, Embryonic Stem,Embryonic Stem Cell,Stem Cell, Embryonic
D054460 rho-Associated Kinases A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES. rho-Associated Kinase,ROCK Protein Kinases,ROCK-I Protein Kinase,ROCK-II Protein Kinase,ROK Kinase,p160 rhoA-Binding Kinase ROKalpha,p160ROCK,rho-Associated Coiled-Coil Containing Protein Kinase 1,rho-Associated Coiled-Coil Containing Protein Kinase 2,rho-Associated Coiled-Coil Kinase,rho-Associated Kinase 1,rho-Associated Kinase 2,rho-Associated Kinase alpha,rho-Associated Kinase beta,rho-Associated Protein Kinase alpha,rho-Associated Protein Kinase beta,rho-Kinase,Coiled-Coil Kinase, rho-Associated,Protein Kinases, ROCK,ROCK I Protein Kinase,ROCK II Protein Kinase,p160 rhoA Binding Kinase ROKalpha,rho Associated Coiled Coil Containing Protein Kinase 1,rho Associated Coiled Coil Containing Protein Kinase 2,rho Associated Coiled Coil Kinase,rho Associated Kinase,rho Associated Kinase 1,rho Associated Kinase 2,rho Associated Kinase alpha,rho Associated Kinase beta,rho Associated Kinases,rho Associated Protein Kinase alpha,rho Associated Protein Kinase beta,rho Kinase

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