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Stem Cell and Development related Pathways

Activation of cAMP-Dependent PKA [ Details | Top ]
cAMP (Cyclic Adenosine 3',5'-monophosphate) is the first identified second messenger, which has a fundamental role in the cellular response to many extracellular stimuli. The cAMP signaling pathway controls a diverse range of cellular processes. Indeed, not only did cAMP provide the paradigm for the second messenger concept, but also provided the paradigm for signaling compartmentalization. The different receptors, chiefly the GPCRs (G-Protein Coupled Receptors), Alpha and Beta-ADRs (Adrenergic Receptors), Growth Factor receptors, CRHR (Corticotropin Releasing Hormone Receptor), GcgR (Glucagon Receptor) ...

Androgen Signaling - New [ Details | Top ]
Androgens mediate a wide range of developmental and physiological responses and are especially important in male sexual differentiation and pubertal sexual maturation, the maintenance of spermatogenesis, and male gonadotropin regulation (Ref.1). The principle steroidal androgens, testosterone and its metabolite DHT (5-Alpha-Dihydrotestosterone), mediate their biological effects predominantly through binding to the AR (Androgen Receptor), an androgen-inducible member of the nuclear receptor superfamily of transcription factors (Ref.2)....

Cytokine Network [ Details | Top ]
The immune system recognizes the presence of pathogens by several proteins that bind to molecules secreted by the pathogen or carried on their surface. The cells responsible for these immune responses include the B-Cells, T-Cells, macrophages, neutrophils, basophils, eosinophils, endothelial cells, or mast cells (Ref.1). These cells have distinct roles in the immune system, and communicate with other immune cells by cytokines, which control proliferation, differentiation and function of cells of the immune system. Furthermore, they are involved in processes of inflammation and in the neuronal, haematopoietic and embryonal development of an organism....

ErbB Family Pathway - New [ Details | Top ]
The ErbB (Erythroblastic Leukemia Viral Oncogene Homolog) or EGF (Epidermal Growth Factor) family of transmembrane RTKs (Receptor Tyrosine Kinases) plays an important role during the growth and development of a number of organs including the heart, the mammary gland, and the central nervous system. In addition, ErbB overexpression is associated with tumorigenesis of the breast, ovaries, brain, and prostate gland. The ErbB family includes four members, EGFR (EGF Receptor)/ErbB1/Her1 (Heregulin-1), ErbB2/Her2 (Heregulin-2), ErbB3/Her3 (Heregulin-3), and ErbB4/Her4 (Heregulin-4) (Ref.1). Two of the family members, ErbB1 and E...

Erythropoietin Pathway - New [ Details | Top ]
Erythropoiesis is one major pathway by which a pluripotent hematopoietic stem cell gives rise to mature end stage cells. Erythropoietin (Epo) is a lineage-specific hematopoietic cell required for survival, proliferation and differentiation of committed erythroid progenitor cells. Its major effects are to promote erythroid differentiation and to initiate hemoglobin synthesis. Therefore, Epo has been identified as the major hormone required for erythropoiesis. Epo exerts its function through the EpoR (Epo Receptor), a member of the classI Cytokine receptor family (Ref.1). Following binding of Epo to its receptor, the recepto...

Factors Promoting Cardiogenesis in Vertebrate - New [ Details | Top ]
Heart is the first organ to form and function in the Embryo, and all subsequent events in the life of the organism depend on the Heart's ability to match its output with the organism's demands for Oxygen and nutrients. Abnormalities in Heart formation, the most common form of Human birth defects, affect nearly 1% of newborns, and their frequency in spontaneously aborted pregnancies is estimated to be tenfold higher. Heart development is an elaborate process requiring Cell specification, Cell differentiation, Cell migration, morphogenesis, and interactions among cells from several embryonic origins. The Heart is formed thro...

FLT3 Signaling - New [ Details | Top ]
FLT3 (Fms-like Tyrosine Kinase-3), also known as FLK2 (Fetal Liver Kinase-2) and STK1 (human Stem Cell Kinase-1) was originally isolated as a hematopoietic progenitor cell-specific kinase, and belongs to the Class-III RTK (Receptor Tyrosine Kinase) family to which c-Fms, c-Kit, and the PDGFR (Platelet Derived Growth Factor Receptor) also belong (Ref.1). Normal expression of FLT3 is restricted to haemopoietic progenitor cells in the bone marrow, thymus and lymph nodes, but is also found on other tissues such as placenta, brain, cerebellum and gonads. Aberrantly expressed FLT3 is observed at high levels in a spectrum of hema...

Hedgehog - New [ Details | Top ]
Controlled cell proliferation is a predominant theme in normal embryonic and post-embryonic development, and, in many instances, cell-type specification and cell proliferation are intimately coupled. Several secreted intercellular signaling proteins that behave as morphogens during pattern formation are also implicated in the regulation of the cell cycle. Hedgehogs (Hhs) are one such class of morphogens that regulate an enormous variety of developmental events in the fly and vertebrate embryo and plays a central role in several cancers....

HGF - New [ Details | Top ]
HGF (Hepatocyte Growth Factor)/SF (Scatter Factor) is a mesenchymal- or stromal-derived multipotent heparan sulfate-binding and dermatan sulfate-binding pleiotropic polypeptide that mediates epithelial-mesenchymal interactions with mitogenic, motogenic and morphogenic activities towards many normal and neoplastic epithelial cells. Initially identified as a potent hepatotrophic factor responsible for vigorous regeneration of the liver, it has now become a well characterized multipotent cytokine with biological functions that reach far beyond the original identifications, operating in virtually every tissue of the body, the...

HIF1Alpha Pathway [ Details | Top ]
The cellular response to O2 (oxygen) is a central process in animal cells and figures prominently in the pathophysiology of several diseases, including cancer, cardiovascular disease, and stroke. This process is coordinated by the HIF (Hypoxia-Inducible Factor) and its regulator, the pVHL (Von Hippel-Lindau tumor suppressor protein). HIF1 is a basic helix-loop-helix transcription factor that transactivates genes encoding proteins that participate in homeostatic responses to hypoxia. It induces expression of proteins controlling glucose metabolism, cell proliferation, and vascularization. Several genes...

Human Early Embryo Development - New [ Details | Top ]
An Embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination. In Humans, it is called an Embryo from the moment of Fertilization until the end of the 8th week of gestational age, whereafter it is instead called a Fetus. In organisms that reproduce sexually, once a Sperm fertilizes an Egg cell, the result is a cell called the Zygote. In animals, the development of the Zygote into an embryo proceeds through specific recognizable stages of Blastula, Gastrula, and Organogenesis. Little is known about the specific genes that regul...

Human Embryonic Stem Cell Pluripotency - New [ Details | Top ]
ESCs (Embryonic Stem Cells) are Pluripotent cells capable of differentiating into any cell type of the body. Only three species of Mammals have yielded long-term cultures of self-renewing ESCs- Mice, Monkeys, and Humans. Human ESCs are derived from Blastocysts, multicellular structures originating from four cleavages of fertilized oocytes. Isolated from the ICM (Inner Cell Mass) of Blastocysts, the ESCs retain properties of self-renewal and the potential to be committed and to differentiate toward most cell lineages. They are able to spontaneously give rise to different progenies of the three embryonic layers, namely, the...

IP3 Pathway [ Details | Top ]
IP3 (Inositol 1,4,5-triphosphate), also known as a second messenger, is a molecule that functions to transfer a chemical signal received by the cell, such as from a hormone, neurotransmitters, growth factors and hypertrophic stimuli such as AngII (Angiotensin-II), Beta-adrenergic receptor agonists, and ET1 (Endothelin-1) to various signaling networks within the cell. IP3 is known to play a crucial role in initiating and propagating these messages; however, the precise mechanism of how IP3 relates to the next element in its signaling pathway, the calcium wave, remains highly controversial. The receptors for IP3, IP3R (IP3 Receptor) constitute a family...

MAPK Signaling [ Details | Top ]
Intracellular signaling cascades are the main routes of communication between the Plasma membrane and regulatory targets in various intracellular compartments. Sequential activation of Kinases is a common mechanism of signal transduction in many cellular processes. During the past decade, several related intracellular signaling cascades have been elucidated, which are collectively known as MAPK (Mitogen-Activated Protein Kinase) signaling cascades. The MAPKs are a group of protein Serine/threonine Kinases that are activated in response to a variety of extracellular stimuli and mediate ....

Nanog in Mammalian ESC Pluripotency - New [ Details | Top ]
ESCs (Embryonic stem cells) are Pluripotent cells derived from the ICM (Inner Cell Mass) of Blastocyst-stage embryos. These cells have two distinctive properties: an unlimited capacity for Self-renewal and Pluripotency. The capability for Self-renewal and the Pluripotency of ESCs seem to be under the control of multiple transcriptional factors, most common among them being Nanog (Nanog homeobox), Oct4 (Octamer Binding Transcription Factor-4) and SOX2 (SRY (Sex Determining Region-Y) Box-2). Functions of these transcription factors depend on the stage of development of a Pluripotent cell, indicating that these factors functi...

RANK Signaling in Osteoclast - New [ Details | Top ]
TNF (Tumor Necrosis Factor) and TNFR (Tumor Necrosis Factor Receptor) family proteins play important roles in the control of cell death, proliferation, autoimmunity, the function of immune cells, or the organogenesis of lymphoid organs. Recently, novel members of this large family have been identified that have critical functions in immunity and that couple lymphoid cells with other organ systems such as bone remodeling and mammary gland formation in pregnancy. Bone remodeling results from the coordinate action of bone resorption by osteoclasts and the formation of new bone by osteoblasts. Regulation of bone remodeling occ...

TGF-Beta Pathway [ Details | Top ]
Cell proliferation in somatic tissues, specification of cell fate during embryogenesis, differentiation and cell death are controlled by a multitude of cell–cell signals and loss of this control has devastating consequences. Prominent among these regulatory signals is the TGF-Beta (Transforming Growth Factor) super family, which comprises a large and diverse group of polypeptide morphogens including the prototype of the family–the TGF-Beta themselves as well as the BMPs (Bone Morphogenetic Proteins), and the GDFs (Growth and Differentiation Factors) (Ref.1). The members of the TGF-Beta family are expressed in distinct temporal...

Toll-Like Receptors Pathway [ Details | Top ]
TLRs (Toll-like receptors) are transmembrane proteins expressed by cells of the innate immune system, which recognize invading microbes and activate signaling pathways that launch immune and inflammatory responses to destroy the invaders. Toll receptors were first identified in Drosophila. In mammals, the TLR family includes eleven proteins (TLR1−TLR11). Recently, two new members, TLR12 and TLR13 have been discovered in mouse, but not much information is known about them. Mammalian TLRs consist of an extracellular portion containing Leucine-rich repeats, a Transmembrane region and a Cytoplasmic tail...

Transcriptional Regulatory Network in Embryonic Stem Cell - New [ Details | Top ]
Stem Cells are undifferentiated cells that can give rise to several lineages of differentiated cell types. They are the founder cells for every organ, tissue and cell in the body. Stem cells are characterized by the ability to self-renew and maintain Pluripotency. These features allow Stem Cells to fulfill their multiple functions, namely to provide enough cells during organogenesis, to control tissue homeostasis and, in addition, to ensure regeneration and repair. ESCs (Embryonic Stem Cells) are derived from the ICM (Inner Cell Mass) of the developing Blastocysts, multicellular structures originating from four (Human) to...

VEGF Pathway [ Details | Top ]
The formation of blood vessels occurs either by in situ differentiation of endothelial cell precursors (Angioblasts) and association of these cells to form primitive vessels, a process called Vasculogenesis, or by growth of preexisting vessels, a process called Angiogenesis. Vasculogenesis establishes the primary vascular plexus of the early embryo, whereas development of blood vessels during later embryogenesis and adult life occurs primarily by Angiogenesis. Angiogenesis is an integral feature of capillary sprouts from preexisting blood vessels. It is typically quiescent in the adult, except for pathological situations...

WNT Signaling [ Details | Top ]
The development of tissues and organs in multicellular organisms is controlled by the interplay of several signaling pathways that cross talk to provide positional information and induce cell fate specification. Together with other families of secreted factors such as TGF-Betas (Transforming Growth Factor-Betas), FGFs (Fibroblast Growth Factors), Hedgehog and Notch proteins, WNT (Wingless-Type MMTV Integration Site Family) Growth Factors are crucially implicated in these processes. The WNT genes encode a large family of secreted protein growth factors that have been identified in animals from Hydra to Human...