Wikipedia

User:Developmentalbio/sandbox

< User:Developmentalbio

Paracrine signaling is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior or differentiation of nearby cells. These paracrine factors diffuse over a relatively short distance (local action), as opposed endocrine factors (hormones which travel considerably longer distances via the circulatory system) and juxtacrine interactions (autocrine signaling). In paracrine signaling, the target cell is near ("para" = near) the signal-releasing cell. Cells that produce paracrine factors secrete them into their immediate extracellular environment. The distance the factors travel distinguishes the type of signaling. However, the exact distance that paracrine factors can travel is not certain.

Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of receptors and pathways. In fact, different organs in the body -even between different species - are known to utilize a similar sets of paracrine factors in differential development. The highly conserved receptor and pathways the paracrine factors utilize can be organized into four major families based on similar structures. They are the fibroblast growth factor (FGF) family, Hedgehog family, Wnt family, and TFG-β superfamily. Binding of a paracrine factor to its respective receptor initiates signal transduction cascades, eliciting different responses.

Developmentalbio (talk) 23:37, 2 April 2013 (UTC)

Paracrine Factors Induce Competent Responders edit

In order for paracrine factors to successfully induce a response in the receiving cell, that cell must be competent -meaning that the appropriate receptors must be available on the cell membrane to receive the signals. Additionally, the responding cell must also have the ability to be mechanistically induced.

Developmentalbio (talk) 23:37, 2 April 2013 (UTC)

Fibroblast Growth Factor (FGF) Family edit

Although the FGF family of paracrine factors have a broad range of functions, major findings support the idea that they primarily stimulate cell functions such as proliferation and differentiation.[1][2]

To fulfill many diverse functions, FGFs can be alternatively spliced or even have different initiation codons to create hundred of different FGF isoforms.[3]

One of the most important functions of the FGF receptors (FGFR) is in limb development. This signaling actually involves nine different alternatively spliced isoforms of the receptor.[4] Fgf8 and Fgf10 are two of the critical players in limb development. For example, in the forelimb initiation and limb growth in mice, axial cues from the intermediate mesoderm produces Tbx5, which then subsequently signals to the same mesoderm to produce Fgf10. In turn, Fgf10 signals to the ectoderm to begin production of Fgf8, which also stimulates the production of Fgf10. This positive feedback loop of paracrine signaling is essential in the production of limbs. Deletion of Fgf10 results in limbless mice.[5]

File:Mouselimb.jpg
Development of limb in mice.

Additionally, paracrine signaling of Fgf is essential in the developing eye of chicks. The fgf8 mRNA becomes localized in what differentiates into the neural retina of the optic cup. These cells are in contact with the outer ectoderm cells, which will eventually become the lens.[5]

Phenotype and survival of mice after knockout of some FGFR genes:[4]

FGFR Knockout Gene Survival Phenotype
Fgf1 Viable Unclear
Fgf3 Viable Inner ear, skeletal (tail) differentiation
Fgf4 Lethal Inner cell mass proliferation
Fgf8 Lethal Gastrulation defect, CNS development, limb development
Fgf10 Lethal Development of multiple organs (including limbs, thymus, pituitary)
Fgf17 Viable Cerebellar Development

Developmentalbio (talk) 03:45, 2 April 2013 (UTC)

Receptor Tyrosine Kinase (RTK) Pathway edit

Paracrine signaling through fibroblast growth factors and its respective receptors utilizes the receptor tyrosine pathway. This signaling pathway has been highly studied, using Drosophila eyes and human cancers.[6]

Binding of FGF to FGFR phosphorylates the previously idle kinase, which activates the RTK pathway. This pathway begins at the cell surface, where a ligand binds to its specific receptor. Ligands that can binds to RTKs include fibroblast growth factors, epidermal growth factors, platelet-derived growth factors, and stem cell factor.[6] This dimerizes the transmembrane receptor to another RTK receptor, which causes the autophosphorylation and subsequent conformational change of the homodimerized receptor. This conformational change activates the dormant kinase of each RTK on the tyrosine residue. Because the receptor spans across the membrane from the extracellular environment, through the lipid bilayer, and into the cytoplasm, the binding of the receptor to the ligand also causes the transphosphorylation of the cytoplasmic domain of the receptor.[7]

Then, an adaptor protein (such as SOS) recognizes the phosphorylated tyrosine on the receptor. This protein functions as a bridge which connects the RTK an intermediate protein (such as GNRP), starting the intracellular signaling cascade. In turn, the intermediate protein stimulates GDP-bound Ras to the activated to GTP-bound Ras. GAP eventually returns Ras to its inactive state. Activation of Ras has the potential to initiate three signaling pathways downstream of Ras: Ras→Raf→MAP kinase pathway, PI3 kinase pathway, and RaI pathway. Each pathway eventually activates transcription factors which enter the nucleus to alter gene expression.[8]

Developmentalbio (talk) 03:45, 2 April 2013 (UTC)

RTK receptor and cancer edit

Paracrine signaling of growth factors between nearby cells has been shown to exasperate carcinogenesis. In fact, mutant forms of a single RTK may play a causal role in very different types of cancer. For example, the Kit proto-oncogene encodes a tyrosine kinase receptor whose ligand is a paracrine protein called stem cell factor (SCF), which is important in hematopoiesis (formation of cells in blood).[9] The Kit receptor and related tyrosine kinase receptors actually are inhibitory and effectively suppresses receptor firing. Mutant forms of the Kit receptor, which fire constitutively in a ligand-independent fashion, are found in a diverse array of cancerous malignancies.[10]

Developmentalbio (talk) 04:21, 2 April 2013 (UTC)

RTK pathway and cancer edit

Research on thyroid cancer has eluciated the theory that paracrine signaling may aid in creating tumor microenvironments. Chemokine transcription is upregulated when Ras is in the GTP-bound state. The chemokines are then released from the cell, free to bind to another nearby cell. Paracrine signaling between neighboring cells creates this positive feedback loop. Thus, the constitutive transcription of upregulated proteins form ideal environments for tumors to arise.[11] Effectively, multiple bindings of ligands to the RTK receptors overstimulates the Ras-Maf-MAP pathway, which overexpresses the mitogenic and invasive capacity of cells.[12]

Developmentalbio (talk) 04:21, 2 April 2013 (UTC)

Jak-STAT Pathway edit

In addition to RTK pathway, fibroblast growth factors can also activate the Jak-STAT signaling cascade. Instead of carrying covalently associated tyrosine kinase domains, Jak-STAT receptors form noncovalent complexes with tyrosine kinases of the Jak (Janus kinase) class. These receptors bind are for erythropoietin (important for erythropoiesis), thrombopoietin (important for platelet formation), and interferon (important for mediating immune cell function).[13]

After dimerization of the cytokine receptors following ligand binding, the Jaks transphosphorylate each other. The resulting phosphotyrosines attract STAT proteins. The STAT proteins dimerize and enter the nucleus to act as transcription factors to alter gene expression.[13] In particular, the STATS transcribe genes that aid in cell proliferation and survival -such as myc.[14]

Phenotype and survival of mice after knockout of some Jak or STAT genes:[15]

Knockout Gene Survival Phenotype
Jak1 Lethal Neurologic Deficits
Jak2 Lethal Failure in erythropoiesis
Stat1 Viable Human dwarfism and craniosynostosis syndromes
Stat3 Lethal Tissue specific phenotypes
Stat4 Viable defective IL-12-driven Th1 differentiation, increased susceptibility to intracellular pathogens

Developmentalbio (talk) 05:45, 2 April 2013 (UTC)

Abberant Jak-STAT Pathway: Bone Mutations edit

The Jak-STAT pathway is also incredibly instrumental in the development of limbs; this pathway regulates bone growth. Paracrine signaling of cytokines induce such developments. However, mutations in this pathway have been implicated in severe forms of dwarfism: thanatophoric dysplasia (lethal) and achondroplasic dwarfism (viable).[16] This is due to a mutation a Fgf gene, causing a premature and constitutive activation of the Stat1 transcription factor. Chondrocyte cell division gets prematurely terminated, resulting in lethal dwarfism. Rib and limb bone growth plate cells do not get transcribed. Thus, the inability of the rib cage to expand prevents the newborn's breathing.[17]

Developmentalbio (talk) 05:45, 2 April 2013 (UTC)

Jak-STAT pathway and Cancer edit

Research on paracrine signaling through the Jak-STAT pathway revealed its potential in activating invasive behavior of ovarian epithelial cells. This epithelial to mesenchymal transition is highly evident in metastasis.[18] Paracrine signaling through the Jak-STAT pathway is necessary in the transition from stationary epithelial cells to mobile mesenchymal cells, which are capable of invading surrounding tissue. Only the Jak-STAT pathway has been found to induce migratory cells.[19]

Developmentalbio (talk) 05:45, 2 April 2013 (UTC)

Hedgehog Family edit

The Hedgehog protein family is involved in induction of cell types and the creation of tissue boundaries and patterning. Hedgehog proteins were first discovered and studied in Drosophila. Hedgehog proteins produce key signals for the establishment of limb and body plan of fuit flies. At least three to "Drosophila" hedgehog homologs have been found in vertebrates: sonic hedgehog, desert hedgehog, and indian hedgehog. Sonic hedgehog (shh) has various roles in vertebrae development, mediaing signaling and regulating the organization of central nervous system, limb, and somite polarity. Desert hedgehog (dhh) is expressed in the Seritoli cells involved in spermatogenesis. Indian hedgehog (ihh) is expressed in the gut and cartilage, important in postnatal bone growth.

Hedgehog Signaling Pathway edit

Hedgehog Signaling Pathway and Cancer edit

Wnt Family edit

The Wnt protein family includes a large number of cytosine-rich glycoproteins. The Wnt proteins activate signal transduction cascades via three different types of pathways, the canonical Wnt pathway, the noncanonical planar cell polarity (PCP) pathway, and the noncanonical Wnt/Ca2+ pathway. The no Wnt proteins appear to control a wide range of developmental processes and have been seen as necessary for control of spindle orientation, cell polarity, cadherin mediated adhesion, and early development of embryos in many different organisms. Current research has indicated that deregulation of Wnt signaling plays a role in tumor formation, because at a cellular level, Wnt proteins often regulated cell proliferation, cell morphology, cell motility, and cell fate. [20]

The Canonical Wnt Pathway edit

In the canonical pathway, Wnt proteins binds to its transmembrane receptor of the Frizzled family of proteins. The binding of Wnt to a Frizzled protein activates the Disheveled protein. In its active state the Disheveled protein inhibits the activity of the glycogen synthase kinase 3 (GSK3) enzyme. Normally active GSK3 prevents the dissociation of β-catenin to the APC protein, which results in β-catenin degradation. Thus inhibited GSK3, allows β-catenin to dissociate from APC, accumulate, and travel to nucleus. In the nucleus β-catenin associates with Lef/Tcf transcription factor, which is already working on DNA as a repressor, inhibiting the transcription of the genes it binds. Binding of β-catenin to Lef/Tcf works as a transcription activator, activating the transcription of the Wnt-responsive genes. [21] [22] [23]

The Noncanonical Wnt Pathways edit

The noncanonical Wnt pathways provide a signal transduction pathway for Wnt that does not involve β-catenin. In the noncanonical pathways, Wnt affects the actin and microtubular cytoskeleton as well as gene transcription.

The Noncanonical Planar Cell Polarity (PCP) Pathway edit

The noncanonical PCP pathway regulates cell morphology, dvision, and movement. Once again Wnt proteins binds to and activates Frizzled so that Frizzled activates a Disheveled protein that is tethered to the plasma membrane through a Prickle protein and transmembrane Stbm protein. The active Disheveled activates RohA GTPase through Disheveled associated activator of morphogenesis 1 (Daam1) and the Rac protein. Active RohA is able to induce cytoskeleton changes by activating Roh-associated kinase (ROCK) and affect gene transcription directly. Active Rac can directly induce cytoskeleton changes and affect gene transcription through activation of JNK. [24] [25] [26]

The Noncanonical Wnt/Ca2+ Pathway edit

The noncanonical Wnt/Ca2+ pathway regulates intracellular calcium levels. Again Wnt binds and activates to Frizzled. In this case however activated Frizzled causes a coupled G-protein to activate a phospholipase (PLC), which interacts with and splits PIP2 into DAG and IP3. IP3 can then bind to a receptor on the endoplasmic reticulum to release intracellular calcium stores, to induce calcium-dependent gene expression. [27] [28] [29]

Wnt Signaling Pathways and Cancer edit

The Wnt signaling pathways are critical in cell-cell singling during normal development and embryogenesis and required for maintenance of adult tissue, therefore it is not difficult to understad why disruption in Wnt signaling pathways can promote human degenerative disease and cancer.

The Wnt signaling pathways are complex, involving many different elements, thus many targets for misregulation. Mutations that cause the constitutive activation of the Wnt signaling pathway lead to tumor formation and cancer. Aberant activation of the wint pathway can lead to increase cell proliferation. Current research is focused on the action of the Wnt signaling pathway on the fate of stem cells, regulating the stem cell choice to proliferate and self renew. This action of Wnt signaling in the possible control and maintenance of stem cells, may provide a possible treatment in cancers exhibiting aberrant Wnt signaling. [30] [31] [32]

chingla 02:02, 3 April 2013 (UTC)

TGF-β Superfamily edit

“TGF” stands for “Transforming Growth Factor,” and the family includes 33 members that encode dimeric, secreted polypeptides that regulate development.[33] Some developmental processes it controls include gastrulation, axis symmetry of the body, organ morphogenesis, and tissue homeostasis in adults.[34]

All TGF-β ligands bind to either Type I or Type II receptors, to create heterotetramic complexes.[35]

Jeenah92 (talk) 06:05, 2 April 2013 (UTC)

TGF-β Pathway edit

The TGF-β pathway regulates many cellular processes in developing embryo and adult organisms, including cell growth, differentiation, apoptosis, and homeostasis. There are five kinds of type II receptors and seven types of type I receptors in humans and other mammals. These receptors are known as “dual-specificity kinases” because their cytoplasmic kinase domain has weak tyrosine kinase activity but strong serine/threonine kinase activity.[36] When a TGF-β superfamily ligand binds to the type II receptor, it recruits a type I receptor and activates it by phosphorylating the serine or threonine residues of its “GS” box.[37] This forms an activation complex that can then phosphorylate SMAD proteins through phosphorylation.

Jeenah92 (talk) 06:05, 2 April 2013 (UTC)

File:Smad signaling pathway.png
SMAD Signaling Pathway Activated by TGF-β

SMAD Pathway edit

There are three classes of SMADs:

  1. Receptor-regulated SMAD (R-SMAD)
  2. Common-mediator SMAD (Co-SMAD)
  3. Inhibitory SMAD (I-SMAD)

Examples of SMADs In Each Class:[38] [39] [40]

Class SMADs
R-SMAD SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8/9
Co-SMAD SMAD4
I-SMAD SMAD6 and SMAD7

The TGF-β Superfamily activates members of the SMAD family, which function as transcription factors. Specifically, the type I receptor, activated by the type II receptor, phosphorylates R-SMADs that then bind to the co-SMAD, SMAD4. The R-SMAD/Co-SMAD forms a complex with importin and enters the nucleus, where they act as transcription factors and either up-regulate or down-regulate in the expression of a target gene.

Specific TGF-β ligands will result in the activation of either the SMAD2/3 or the SMAD1/5 R-SMADs. For instance, when activin, Nodal, or TGF-β ligand binds to the receptors, the phosphorylated receptor complex can activate SMAD2 and SMAD3 through phosphorylation. However, when a BMP ligand binds to the receptors, the phosphorylated receptor complex activates SMAD1 and SMAD5. Then, the Smad2/3 or the Smad1/5 complexes form a dimer complex with SMAD4 and become transcription factors. Though there are many R-SMADs involved in the pathway, there is only one co-SMAD, SMAD4.[41]

Jeenah92 (talk) 06:05, 2 April 2013 (UTC)

Non-SMAD Pathway edit

Non-Smad signaling proteins contribute to the responses of the TGF-β pathway in three ways. First, non-Smad signaling pathways phosphorylate the Smads. Second, Smads directly signal to other pathways by communicating directly with with other signaling proteins, such as kinases. Finally, the TGF-β receptors directly phosphorylate non-Smad proteins.[42]

Members of TGF-β Superfamily edit

1. TGF-β Family edit

This family includes TGF-β1, TGF-β2, TGF-β3, and TGF-β5. They are involved in positively and negatively regulation of cell division, the formation of the extracellular matrix between cells, apoptosis, and embryogenesis. They bind to TGF-β type II receptor (TGFBRII).

TGF-β1 stimulates the synthesis of collagen and fibronectin and inhibits the degradation of the extracellular matrix degradation. Ultimately, it increases the production of extracellular matrix by epithelial cells.[43] TGF-β proteins regulate epithelia by controlling where and when they branch to form kidney, lung, and salivary gland ducts.[44]

Jeenah92 (talk) 06:05, 2 April 2013 (UTC)

2. Bone Morphogenetic Protein (BMPs) Family edit

Members of the BMP family were originally found to induce bone formation, as their name suggests. However, BMPs are very multifunctional and can also regulate apoptosis, cell migration, cell division, and differentiation. They also specify the anterior/posterior axis, induce growth, and regulate homeostatis.[45]

The BMPs bind to the bone morphogenetic protein receptor type II (BMPR2). Some of the proteins of the BMP family are BMP4 and BMP7. BMP4 promotes bone formation, causes cell death, or signals the formation of epidermis, depending on the tissue it is acting on. BMP7 is crucial for kidney development, sperm synthesis, and neural tube polarization. Both BMP4 and BMP7 regulate mature ligand stability and processing, including degrading ligands in lysosomes.[46] BMPs act by diffusing from the cells that create them.[47]

Jeenah92 (talk) 06:05, 2 April 2013 (UTC)

Other Members of TFG-β Superfamily edit

Jeenah92 (talk) 06:05, 2 April 2013 (UTC)

Summary table edit

TGF Beta superfamily ligand Type II Receptor Type I Receptor R-SMADs Co-SMAD Ligand Inhibitors
Activin A ACVR2A ACVR1B (ALK4) SMAD2, SMAD3 SMAD4 Follistatin
GDF1 ACVR2A ACVR1B (ALK4) SMAD2, SMAD3 SMAD4
GDF11 ACVR2B ACVR1B (ALK4), TGFβRI (ALK5) SMAD2, SMAD3 SMAD4
Bone morphogenetic proteins BMPR2 BMPR1A (ALK3), BMPR1B (ALK6) SMAD1 SMAD5, SMAD8 SMAD4 Noggin, Chordin, DAN
Nodal ACVR2B ACVR1B (ALK4), ACVR1C (ALK7) SMAD2, SMAD3 SMAD4 Lefty
TGFβs TGFβRII TGFβRI (ALK5) SMAD2, SMAD3 SMAD4 LTBP1, THBS1, Decorin

Examples edit

Growth factor and clotting factors are paracrine signaling agents. The local action of growth factor signaling plays an especially important role in the development of tissues. Also, retinoic acid, the active form of vitamin A, functions in a paracrine fashion to regulate gene expression during embryonic development in higher animals.[49] In insects, Allatostatin controls growth though paracrine action on the corpora allata.[citation needed]

In mature organisms, paracrine signaling is involved in responses to allergens, tissue repair, the formation of scar tissue, and blood clotting.[citation needed]

See also edit

References edit

  1. ^ Gospodarowicz, D., Ferrarra N., Schweigerer L., Neufeld G. (May 1987). "Structural Characterization and Biological Functions of Fibroblast Growth Factor". Endocrine Reviews. 8 (2): 95–114. doi:10.1210/edrv-8-2-95. PMID 2440668. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)CS1 maint: multiple names: authors list (link)
  2. ^ Rifkin D.B. & Moscatelli D. (July 1989). "Recent Developments in the Cell Biology of Basic Fibroblast Growth Factor" (PDF). Mini-Review. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  3. ^ Lappi D.A. (October 1995). "Tumor targeting through fibroblast growth factor receptors". Seminars in Cancer Biology. 6 (5): 279–288. doi:10.1006/scbi.1995.0036. PMID 8562905. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  4. ^ a b Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F., Gao G., Goldfarb M. (June 1996). "Receptor Specificity of the Fibroblast Growth Factor Family". The Journal of Biological Chemistry. 271 (25): 15292–15297. doi:10.1074/jbc.271.25.15292. PMID 8663044. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "Ornitz" was defined multiple times with different content (see the help page).
  5. ^ a b Logan M. (December 2003). "Tumor targeting through fibroblast growth factor receptors". Development. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  6. ^ a b Fantl W.J., Johnson D.E., Williams L.T. (1993). "Signaling by receptor tyrosine kinases". Annual Reviews. 62: 453–481. doi:10.1146/annurev.bi.62.070193.002321. PMID 7688944. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)CS1 maint: multiple names: authors list (link)
  7. ^ Yarden Y. (1988). "Growth Factor Receptor Tyrosine". Annual Reviews of Biochemistry. 62: 453–481. doi:10.1146/annurev.bi.62.070193.002321. PMID 7688944. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  8. ^ Katz M.E. & McCormick F. (February 1997). "Signal transduction from multiple Ras effectors". Current Opinion in Genetics & Development. 7 (1): 75–79. doi:10.1016/S0959-437X(97)80112-8. PMID 9024640. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  9. ^ Zsebo K.M. (October 1990). "Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor". Cell. 63 (1): 213–224. doi:10.1016/0092-8674(90)90302-U. PMID 1698556. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  10. ^ Rönnstrand L. (April 2004). "Signal transduction via the stem cell factor receptor/c-Kit" (PDF). Cellular and Molecular Life Sciences. 61 (19–20): 2535–2548. doi:10.1007/s00018-004-4189-6. PMID 15526160. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  11. ^ Mellilo R.M. (April 2005). "The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells". The Journal of Clinical Investigation. 115 (4): 1068–1081. doi:10.1172/JCI200522758. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  12. ^ Kolch W. (April 2005). "Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions" (PDF). Biochemistry Journal. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  13. ^ a b Aaronson D.S. & Horvath C.M. (May 2002). "A Road Map for Those Who Don't Know JAK-STAT". Science. 296 (5573): 1653–1655. doi:10.1126/science.1071545. PMID 12040185. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  14. ^ Rawlings S.J., Rosler K.M., Harrison D.A. (March 2004). "The JAK/STAT signaling pathway". Journal of Cell Science. 117 (Pt 8): 1281–1283. doi:10.1242/jcs.00963. PMID 15020666. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)CS1 maint: multiple names: authors list (link)
  15. ^ O’Shea J.J., Gadina M., Schreiber R.D. (April 2002). "Cytokine Signaling in 2002: New Surprises in the Jak/Stat Pathway" (PDF). Cell. 109 Suppl: S121-31. doi:10.1016/S0092-8674(02)00701-8. PMID 11983158. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)CS1 maint: multiple names: authors list (link)
  16. ^ Bonaventure J., Rousseau, F., Legeai-Malle L., Le Merrer M., Munnich A., Maroteaux P. (1996). "Common Mutations in the Fibroblast Growth Factor Receptor 3 (FGFR 3) Gene Account for Achondroplasia, Hypochondroplasia, and Thanatophoric Dwarfism". American Journal of Medical Genetics. 63 (1): 148–154. doi:10.1002/(SICI)1096-8628(19960503)63:1<148::AID-AJMG26>3.0.CO;2-N. PMID 8723101. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)CS1 maint: multiple names: authors list (link)
  17. ^ Shiang R., Thompson L.M., Zhu Y., Church D.M., Fielder T.J., Bocian M., Winokur S.T., Wasmuth J.J. (June 1994). "Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia". Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help); Cite journal requires |journal= (help)CS1 maint: multiple names: authors list (link)
  18. ^ Kalluri R. & Weinberg R.A. (2009). "The basics of epithelial-mesenchymal transition". The Journal of Clinical Investigation. 119 (6): 1420–1428. doi:10.1172/JCI39104. PMC 2689101. PMID 19487818. Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help)
  19. ^ Silve D.L. & Montell D.J. (December 2001). "Paracrine Signaling through the JAK/STAT Pathway Activates Invasive Behavior of Ovarian Epithelial Cells in Drosophila". Retrieved 20013-04-01. {{cite journal}}: Check date values in: |accessdate= (help); Cite journal requires |journal= (help)
  20. ^ Cadigan, K.M. & Nusse, R. (1997) "Wnt signaling: a common theme in animal development?", "Genes & Development" Retrieved 19 March 2013.
  21. ^ Dale, T.C. (1998) "Signal transduction by the Wnt family of ligands", "Biochemical Journal" Retrieved 19 March 2013.
  22. ^ Chen, X., Yang, J., Evans, P.M., Lui, C. (July 2008) "Wnt signaling: the good and the bad", "Acta Biochim Biophys Sin (Shanghai)" Retrieved 19 March 2013.
  23. ^ Komiya, Y. & Raymond H. (April/ May/ June 2008) "Wnt signal transduction pathways.", "Organogenesis" 4.2: 68-75.
  24. ^ Dale, T.C. (1998) "Signal transduction by the Wnt family of ligands", "Biochemical Journal" Retrieved 19 March 2013.
  25. ^ Chen, X., Yang, J., Evans, P.M., Lui, C. (July 2008) "Wnt signaling: the good and the bad", "Acta Biochim Biophys Sin (Shanghai)" Retrieved 19 March 2013.
  26. ^ Komiya, Y. & Raymond H. (April/ May/ June 2008) "Wnt signal transduction pathways.", "Organogenesis" 4.2: 68-75.
  27. ^ Dale, T.C. (1998) "Signal transduction by the Wnt family of ligands", "Biochemical Journal" Retrieved 19 March 2013.
  28. ^ Chen, X., Yang, J., Evans, P.M., Lui, C. (July 2008) "Wnt signaling: the good and the bad", "Acta Biochim Biophys Sin (Shanghai)" Retrieved 19 March 2013.
  29. ^ Komiya, Y. & Raymond H. (April/ May/ June 2008) "Wnt signal transduction pathways.", "Organogenesis" 4.2: 68-75.
  30. ^ Logan, C.Y. & Nusse, R. (July 2004) "The Wnt Signaling Pathway in Development and Disease", "Annual Review Cell Dev. Biol." Retrieved 1 April 2013.
  31. ^ Lustig, B. & Behrens, J. (April 2003) "The Wnt signaling pathway and its role in tumor development", "Journal of Cancer Research and Clinal Oncology" Retrieved 1 April 2013
  32. ^ Neth, P., Ries, C., Karow, M., Egea, V., Ilmer, M., Jochum, M. "The Wnt Signal Transduction Pathway in Stem Cells and Cancer Cells: Influence on Cellular Invasion", "Stem Cell Reviews" Retrieved 20 March 2013
  33. ^ Bandyopadhyay, Amitabha, et al. "Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis." PLoS genetics 2.12 (2006): e216.
  34. ^ Attisano, Liliana, and Jeffrey L. Wrana. "Signal transduction by the TGF-beta superfamily." Science Signaling 296.5573 (2002): 1646.
  35. ^ Wrana, J. L., Ozdamar, B., Le Roy, C. and Benchabane, H. (2008). Signaling receptors of the TGF-β family. In The TGF-β Family (ed. R. Derynck and K. Miyazono), pp. 179-202. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
  36. ^ Dijke, P. and Heldin, C. H. (2006). The Smad family. In Smad Signal Transduction, vol.5 (ed. P. ten Dijke and C. H. Heldin), pp.1 -13. Dordrecht, The Netherlands: Springer.
  37. ^ Moustakas, Aristidis. "Smad signalling network." Journal of cell science 115.17 (2002): 3355-3356.
  38. ^ Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, Rigotti DJ, Kyin S, Muir TW, Fairman R, Massagué J, Shi Y (December 2001). "Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling". Mol. Cell. 8 (6): 1277–89. doi:10.1016/S1097-2765(01)00421-X. PMID 11779503.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  39. ^ Shi Y, Hata A, Lo RS, Massagué J, Pavletich NP (July 1997). "A structural basis for mutational inactivation of the tumour suppressor Smad4". Nature. 388 (6637): 87–93. doi:10.1038/40431. PMID 9214508.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  40. ^ Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". EMBO J. 20 (15): 4132–42. doi:10.1093/emboj/20.15.4132. PMC 149146. PMID 11483516.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  41. ^ Schmierer, B. and Hill, C. S. (2007). TGFβ-SMAD signal transduction: molecular specificity and functional flexibility. Nat. Rev. Mol. Cell. Biol. 8, 970-982.
  42. ^ Moustakas, Aristidis, and Carl-Henrik Heldin. "Non-Smad TGF-β signals."Journal of cell science 118.16 (2005): 3573-3584.
  43. ^ Wrana, J. L., Ozdamar, B., Le Roy, C. and Benchabane, H. (2008). Signaling receptors of the TGF-β family. In The TGF-β Family (ed. R. Derynck and K. Miyazono), pp. 179-202. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
  44. ^ Wrana, J. L., Ozdamar, B., Le Roy, C. and Benchabane, H. (2008). Signaling receptors of the TGF-β family. In The TGF-β Family (ed. R. Derynck and K. Miyazono), pp. 179-202. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
  45. ^ Bandyopadhyay A, Tsuji K, Cox K, Harfe BD, Rosen V, et al. (2006) Genetic Analysis of the Roles of BMP2, BMP4, and BMP7 in Limb Patterning and Skeletogenesis. PLoS Genet 2(12): e216. doi:10.1371/journal.pgen.0020216
  46. ^ Bandyopadhyay, Amitabha, et al. "Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis." PLoS genetics 2.12 (2006): e216.
  47. ^ Ohkawara, Bisei, et al. "Action range of BMP is defined by its N-terminal basic amino acid core." Current biology 12.3 (2002): 205-209.
  48. ^ Munir S, Xu G, Wu Y, Yang B, Lala PK, Peng C (July 2004). "Nodal and ALK7 inhibit proliferation and induce apoptosis in human trophoblast cells". J. Biol. Chem. 279 (30): 31277–86. doi:10.1074/jbc.M400641200. PMID 15150278
  49. ^ Duester, G (September 2008). "Retinoic acid synthesis and signaling during early organogenesis". Cell. 134 (6): 921–31. doi:10.1016/j.cell.2008.09.002. PMC 2632951. PMID 18805086.{{cite journal}}: CS1 maint: date and year (link)

External links edit

Category:Signal transduction

Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Developmentalbio/sandbox&oldid=1168383041"