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This is from another of the Ingber Reviews that I mentioned above
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so is this oneCell Distortion
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From Integrin signaling's potential for mediating gene expression in hypertrophying skeletal muscle
Signaling pathways that can be activated in skeletal muscle by integrin-mediated signaling. An overload stimulus can potentially activate many different signaling cascades in skeletal muscle. However, how all these signaling pathways are integrated into a growth response is not completely understood. Integrin/RhoA signaling in skeletal muscle is an excellent candidate for integrating at least some of these events for the induction of hypertrophy. FAK, focal adhesion kinase; PI-3 kinase, phosphatidylinositol-3 kinase; JNK, c-Jun NH2-terminal kinase; PIP2, L--phosphatidylinositol 4,5-diphosphate.
Signaling pathways that can be activated in skeletal muscle by integrin-mediated signaling. An overload stimulus can potentially activate many different signaling cascades in skeletal muscle. However, how all these signaling pathways are integrated into a growth response is not completely understood. Integrin/RhoA signaling in skeletal muscle is an excellent candidate for integrating at least some of these events for the induction of hypertrophy. FAK, focal adhesion kinase; PI-3 kinase, phosphatidylinositol-3 kinase; JNK, c-Jun NH2-terminal kinase; PIP2, L--phosphatidylinositol 4,5-diphosphate.
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From the same
Several levels of cellular regulation appear critical for large overload-induced increases in skeletal muscle mass. These points of regulation may have varying degrees of importance for inducing protein synthesis during the time course of overload-induced growth, especially in animal models of extreme hypertrophy. It is critically important to define how different cellular events are integrated to allow for a sequential growth response in skeletal muscle. eIFs, eukaryotic initiation factors.
Several levels of cellular regulation appear critical for large overload-induced increases in skeletal muscle mass. These points of regulation may have varying degrees of importance for inducing protein synthesis during the time course of overload-induced growth, especially in animal models of extreme hypertrophy. It is critically important to define how different cellular events are integrated to allow for a sequential growth response in skeletal muscle. eIFs, eukaryotic initiation factors.
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This relates more to what kicks off MAPK cascading.
From Integrins Regulate the Linkage between Upstream and Downstream Events in G Protein-coupled Receptor Signaling to Mitogen-activated Protein Kinase
Stimulation of endogenous P2Y (Gq/11)-coupled receptors results in anchorage-independent accumulation of inositol phosphates and release of intracellular calcium, and anchorage-dependent activation of both MEK and MAPK. The point of anchorage regulation lies below the release of intracellular calcium and above the activation of MEK. This pathway is independent of tyrosine kinases and Raf and involves PKC. The point of anchorage regulation may involve a MEKK or another component (X), possibly a calcium-activated kinase.
From Integrins Regulate the Linkage between Upstream and Downstream Events in G Protein-coupled Receptor Signaling to Mitogen-activated Protein Kinase
Stimulation of endogenous P2Y (Gq/11)-coupled receptors results in anchorage-independent accumulation of inositol phosphates and release of intracellular calcium, and anchorage-dependent activation of both MEK and MAPK. The point of anchorage regulation lies below the release of intracellular calcium and above the activation of MEK. This pathway is independent of tyrosine kinases and Raf and involves PKC. The point of anchorage regulation may involve a MEKK or another component (X), possibly a calcium-activated kinase.
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From Differential gene expression in the rat soleus muscle during early work overload-induced hypertrophy
Scheme depicting the proposed molecular events and related functional alterations occurring in skeletal muscle in response to work overload
Scheme depicting the proposed molecular events and related functional alterations occurring in skeletal muscle in response to work overload
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The PI(3)K/Akt(PKB)/mTOR pathway is a
crucial regulator of skeletal muscle
hypertrophy/atrophy
Application of IGF-I to C2C12 myotube cultures induced both increased width and phosphor-ylation of downstream targets of Akt (p70S6 kinase, p70S6K; PHAS-1/4E-BP1; GSK3) but did NOT activate the calcineurin pathway.
Treatment with rapamycin almost completely prevented increase in width of C2C12 myotubes.
Treatment with cyclosporin or FK506 does not prevent myotube growth in vitro or compensatory hypertrophy in vivo
Recovery of muscle weight after following reloading is blocked by rapamycin but not cyclosporin.
crucial regulator of skeletal muscle
hypertrophy/atrophy
Application of IGF-I to C2C12 myotube cultures induced both increased width and phosphor-ylation of downstream targets of Akt (p70S6 kinase, p70S6K; PHAS-1/4E-BP1; GSK3) but did NOT activate the calcineurin pathway.
Treatment with rapamycin almost completely prevented increase in width of C2C12 myotubes.
Treatment with cyclosporin or FK506 does not prevent myotube growth in vitro or compensatory hypertrophy in vivo
Recovery of muscle weight after following reloading is blocked by rapamycin but not cyclosporin.
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From the Book
Molecular Biology of the Cell
Figure 17-44. One way in which growth factors promote cell growth. In this simplified scheme, activation of cell-surface receptors leads to the activation of PI 3-kinase, which promotes protein synthesis, at least partly through the activation of eIF4E and S6 kinase. Growth factors also inhibit protein breakdown (not shown) by poorly understood pathways.
Molecular Biology of the Cell
Figure 17-44. One way in which growth factors promote cell growth. In this simplified scheme, activation of cell-surface receptors leads to the activation of PI 3-kinase, which promotes protein synthesis, at least partly through the activation of eIF4E and S6 kinase. Growth factors also inhibit protein breakdown (not shown) by poorly understood pathways.
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Figure 17-41. A simplified model of one way that mitogens stimulate cell division. The binding of mitogens to cell-surface receptors leads to the activation of Ras and a MAP kinase cascade. One effect of this pathway is the increased production of the gene regulatory protein Myc. Myc increases the transcription of several genes, including the gene encoding cyclin D and a gene encoding a subunit of the SCF ubiquitin ligase. The resulting increase in G1-Cdk and G1/S-Cdk activities promotes Rb phosphorylation and activation of the gene regulatory protein E2F, resulting in S-phase entry (see Figure 17-30). Myc may also promote E2F activity directly by stimulating the transcription of the E2F gene. Although, for simplicity, Myc is shown as a monomer, it functions as a heterodimer with another protein called Max.
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Figure 7-72. Role of the myogenic regulatory proteins in muscle development. (A) The effect of expressing the MyoD protein in fibroblasts. As shown in this immunofluorescence micrograph, fibroblasts from the skin of a chick embryo have been converted to muscle cells by the experimentally induced expression of the myoD gene. The fibroblasts that have been induced to express the myoD gene have fused to form elongated multinucleate muscle-like cells, which are stained green with an antibody that detects a muscle-specific protein. Fibroblasts that do not express the myoD gene are barely visible in the background. (B) Simplified scheme for some of the gene regulatory proteins involved in skeletal muscle development. The commitment of mesodermal progenitor cells to the muscle-specific pathway involves the synthesis of the four myogenic gene regulatory proteins, MyoD, Myf5, myogenin and Mrf4. These proteins directly activate transcription of muscle structural genes as well as the MEF2 gene, which encodes an additional gene regulatory protein. Mef2 acts in combination with the myogenic proteins to further activate transcription of muscle structural genes and to create a positive feedback loop that acts to maintain transcription of the myogenic genes. (A, courtesy of Stephen Tapscott and Harold Weintraub; B, adapted from J.D. Molkentin and E.N. Olson, Proc. Natl. Acad. Sci. USA 93:93669373, 1996.)
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Figure 7-36. Summary of the mechanisms by which specific gene regulatory proteins control gene transcription in procaryotes. (A) Negative regulation; (B) positive regulation. Note that the addition of an "inducing" ligand can turn on a gene either by removing a gene repressor protein from the DNA (upper left panel) or by causing a gene activator protein to bind (lower right panel). Likewise, the addition of an "inhibitory" ligand can turn off a gene either by removing a gene activator protein from the DNA (upper right panel) or by causing a gene repressor protein to bind (lower left panel).
Note: A procaryote is a single-celled microorganism whose cells lack a well-defined, membrane-enclosed nucleus. The procaryotes comprise two of the major domains of living organismsthe Bacteria and the Archaea. And even though they are not as complicated as a muscle cell, I assumed that the gene regulation would be close if not the same, but we all know what happens when you ASSUME
, so if I am wrong please correct me.
Note: A procaryote is a single-celled microorganism whose cells lack a well-defined, membrane-enclosed nucleus. The procaryotes comprise two of the major domains of living organismsthe Bacteria and the Archaea. And even though they are not as complicated as a muscle cell, I assumed that the gene regulation would be close if not the same, but we all know what happens when you ASSUME
, so if I am wrong please correct me.
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Figure 3-68. The activation of a Src-type protein kinase by two sequential events
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Figure 3-72. A comparison of the two major intracellular signaling mechanisms in eucaryotic cells. In both cases, a signaling protein is activated by the addition of a phosphate group and inactivated by the removal of this phosphate. To emphasize the similarities in the two pathways, ATP and GTP are drawn as APPP and GPPP, and ADP and GDP as APP and GPP, respectively. As shown in Figure 3-63, the addition of a phosphate to a protein can also be inhibitory.
Now compile all of it into a single chart
I have a diagram of an adipocyte in front of me, and am currently working my way through about three different pathways from calcium, angiotensin and acylation stimulating protein, and seeing where they tie up in the middle.
which is almost as stupid as the theory of hypertrophy within a myocyte, because its hypertrophy of an adipocyte
I have a diagram of an adipocyte in front of me, and am currently working my way through about three different pathways from calcium, angiotensin and acylation stimulating protein, and seeing where they tie up in the middle.
which is almost as stupid as the theory of hypertrophy within a myocyte, because its hypertrophy of an adipocyte
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That's what I have been working on for about month, haphazardly working on obviously, but I do plan on finishing it.
Aaron have you thought of posting yours? I think it would be great if you would, maybe start a flow chart thread about Metabolism.
Also if you or anyone else who knows wishes to add to this one please do, I am only self-taught (unlike you and MikeyNov) so there are limits to my understanding. Any help would be appreciated.
Aaron have you thought of posting yours? I think it would be great if you would, maybe start a flow chart thread about Metabolism.
Also if you or anyone else who knows wishes to add to this one please do, I am only self-taught (unlike you and MikeyNov) so there are limits to my understanding. Any help would be appreciated.
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[b said:Quote[/b] (Aaron_F @ Jan. 12 2005,5:48)]Unfortuantely, its not something that I can do at this stage, as I dont own it
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I like how this one spelled out which phosphorlyation events either turned on or off downstream targets, it's from.
Molecular and cellular determinants of skeletal muscle atrophy and hypertrophy.Sartorelli V, Fulco M.
Fig. 1.
The IGF-1 pathway is involved in muscle atrophy and hypertrophy. Upon IGF-1 binding, the IGFR is phosphorylated. The phosphorylated receptor recruits and phosphorylates the IRS1, which activates PI3K. PI3K transfers a phosphate group to the membrane-bound PIP2 to generate PIP3. PIP3 serves as a nucleation site for Akt1 and PDK-1. PDK-1 phosphorylates and activates Akt1, which, in turn, catalyzes the transfer of phosphate groups to several substrates. Akt-mediated phosphorylation of the FOXO transcription factors promotes their cytoplasmic retention and functional inactivation through interaction with the 14-3-3 proteins. Because the FOXO proteins stimulate the transcription of the atrophy-promoting factor MAFbx, FOXO inactivation prevents muscle atrophy. Akt phosphorylates and inhibits GSK-3ß, which activates the eukaryotic translation factor eIF-2B and increases protein synthesis. The mTOR is also a phosphorylation substrate for Akt. With the assistance of the interacting protein Raptor, phosphorylated mTOR promotes phosphorylation and inhibition of 4EBP1. Also, mTOR promotes protein synthesis by relieving 4EBP1-mediated inhibition of eIF-4B. When phosphorylated by mTOR, the ribosomal p70S6K becomes activated and increases protein synthesis. Green arrows indicate phosphorylation events that activate the substrate, whereas red arrows point at phosphorylations that result in substrate inactivation.
Molecular and cellular determinants of skeletal muscle atrophy and hypertrophy.Sartorelli V, Fulco M.
Fig. 1.
The IGF-1 pathway is involved in muscle atrophy and hypertrophy. Upon IGF-1 binding, the IGFR is phosphorylated. The phosphorylated receptor recruits and phosphorylates the IRS1, which activates PI3K. PI3K transfers a phosphate group to the membrane-bound PIP2 to generate PIP3. PIP3 serves as a nucleation site for Akt1 and PDK-1. PDK-1 phosphorylates and activates Akt1, which, in turn, catalyzes the transfer of phosphate groups to several substrates. Akt-mediated phosphorylation of the FOXO transcription factors promotes their cytoplasmic retention and functional inactivation through interaction with the 14-3-3 proteins. Because the FOXO proteins stimulate the transcription of the atrophy-promoting factor MAFbx, FOXO inactivation prevents muscle atrophy. Akt phosphorylates and inhibits GSK-3ß, which activates the eukaryotic translation factor eIF-2B and increases protein synthesis. The mTOR is also a phosphorylation substrate for Akt. With the assistance of the interacting protein Raptor, phosphorylated mTOR promotes phosphorylation and inhibition of 4EBP1. Also, mTOR promotes protein synthesis by relieving 4EBP1-mediated inhibition of eIF-4B. When phosphorylated by mTOR, the ribosomal p70S6K becomes activated and increases protein synthesis. Green arrows indicate phosphorylation events that activate the substrate, whereas red arrows point at phosphorylations that result in substrate inactivation.
