The power and versatility of TGFs action lay in the fact in there no one TGF, but a family of TGFs with numbers attached to them (TGF1,2,3 etc). And each member having a different effect, some being completely opposed to each other but circumstances (including location) in the life of the cell will determine which family member will be at work at a given time.
ie.
Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach*
Franck Verrecchia‡et al!"Members of the TGF-β1superfamily (activin, bone morphogenic proteins, TGF-βs, and decapentaplegic) are multifunctional cytokines that control various aspects of cell growth and differentiation and play an essential role in embryonic development, tissue repair, or immune homeostasis (1, 2). In addition, TGF-β is the prototypic fibrogenic cytokine, enhancing extracellular matrix (ECM) gene expression and down-regulating that of matrix-degrading enzymes. Increased expression of TGF-β is often associated with fibrotic states and abnormal accumulation of ECM proteins in affected tissues (3-6). The TGF-βs signal via serine/threonine kinase transmembrane receptors, which phosphorylate cytoplasmic mediators of the Smad family (7-9). The ligand-specific Smad1, Smad2, Smad3, and Smad5 interact directly with, and are phosphorylated by, activated TGF-β receptors type I. Smad1 and Smad5 are specific for bone morphogenic proteins, whereas Smad2 and Smad3 can be activated by both TGF-β and activin receptors. Receptor-activated Smads are kept in the cytoplasm in the basal state bound to the protein SARA (Smad anchor forreceptor activation) (10). Upon phosphorylation at their SSXS carboxyl-terminal motif, they are released from SARA and form heteromeric complexes with Smad4, a common mediator for all Smad pathways. The resulting Smad heterocomplexes are then translocated into the nucleus where they activate target genes, binding DNA either directly or in association with other transcription factors. Members of the third group of Smads, the inhibitory Smads, Smad6 and Smad7, prevent phosphorylation and/or nuclear translocation of receptor-associated Smads (7-9)."=============================================
IE.WATCH "ACTIVIN" BECAUSE
"
The ACVRL1 gene provides instructions
for making a protein called activin receptor-like kinase 1. This
protein is found on the surface of cells, especially in the lining of
developing arteries.
The ACVRL1 protein is a receptor. It acts as a "lock" waiting for a specific protein, called its ligand, to serve as the "key." In the case of the ACVRL1 protein, the ligand is called transforming growth factor beta. The interaction between these proteins plays a role in the development of blood vessels. In particular, this protein interaction is involved in the specialization of new blood vessels into arteries or veins."
ACVR2A has been shown to interact with INHBA,[4][5] SYNJ2BP[6][7] and ACVR1B.[8][9]
=================================================THROUGH IN SYNJ2BP,
SYNJ2BP has been shown to interact with LRP2,[3] ACVR2B,[1] ACVR2A[1][4] and LRP1.[3]
=========================================================THROUGH LRP1
LRP1 has been shown to interact with Apolipoprotein E,[11][12] Lipoprotein lipase,[13][14][15] Urokinase receptor,[16] MAPK8IP2,[17] Tissue plasminogen activator,[18][19] Thrombospondin 1,[20][21][22] SYNJ2BP,[17] DLG4,[17] NOS1AP,[17] calreticulin,[23] APBB1,[24] ITGB1BP1,[17] MAPK8IP1,[17] GIPC1[17] and SHC1.[25][26]
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene.[1] SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells.
==============================================================
THAT'S HOW YOU FIND OUT HOW TGF WORKS TO BLOCK APOPTOSIS!
ACTIVIN IS A MALFORMATION INDUCING GENE
IT IS BOUND TO INHIBIN A BAD PROGNOSIS BIOMARKER IN GERM CELL CANCER
IT HAS A LINK TO ANGIOGENESIS (DOES AVASTIN WORKS HERE?)
WANT TO GO AFTER SHC1, BE MY GUEST!
IF WE ARE TREATING CANCER PATIENTS LIKE WE DO TODAY WITHOUT LOOKING AT THE CANCER CYTOKINES, WE ARE MISSING THE BIG PICTURE!
WE THANK THE NIH, MDHONORS, AND WIKIPEDIA FOR THEIR CONTRIBUTION TO SCIENCE AND PROGRESS TOWARD THE CURE (WE HOLD OFF ON OTHER FUNDING SOURCES )
The ACVRL1 protein is a receptor. It acts as a "lock" waiting for a specific protein, called its ligand, to serve as the "key." In the case of the ACVRL1 protein, the ligand is called transforming growth factor beta. The interaction between these proteins plays a role in the development of blood vessels. In particular, this protein interaction is involved in the specialization of new blood vessels into arteries or veins."
ACVR2A has been shown to interact with INHBA,[4][5] SYNJ2BP[6][7] and ACVR1B.[8][9]
=================================================THROUGH IN SYNJ2BP,
SYNJ2BP has been shown to interact with LRP2,[3] ACVR2B,[1] ACVR2A[1][4] and LRP1.[3]
=========================================================THROUGH LRP1
LRP1 has been shown to interact with Apolipoprotein E,[11][12] Lipoprotein lipase,[13][14][15] Urokinase receptor,[16] MAPK8IP2,[17] Tissue plasminogen activator,[18][19] Thrombospondin 1,[20][21][22] SYNJ2BP,[17] DLG4,[17] NOS1AP,[17] calreticulin,[23] APBB1,[24] ITGB1BP1,[17] MAPK8IP1,[17] GIPC1[17] and SHC1.[25][26]
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene.[1] SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells.
==============================================================
THAT'S HOW YOU FIND OUT HOW TGF WORKS TO BLOCK APOPTOSIS!
ACTIVIN IS A MALFORMATION INDUCING GENE
IT IS BOUND TO INHIBIN A BAD PROGNOSIS BIOMARKER IN GERM CELL CANCER
IT HAS A LINK TO ANGIOGENESIS (DOES AVASTIN WORKS HERE?)
WANT TO GO AFTER SHC1, BE MY GUEST!
IF WE ARE TREATING CANCER PATIENTS LIKE WE DO TODAY WITHOUT LOOKING AT THE CANCER CYTOKINES, WE ARE MISSING THE BIG PICTURE!
WE THANK THE NIH, MDHONORS, AND WIKIPEDIA FOR THEIR CONTRIBUTION TO SCIENCE AND PROGRESS TOWARD THE CURE (WE HOLD OFF ON OTHER FUNDING SOURCES )
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