SMAD-signaalitiestä ja TGF-beta reseptorista . TGFbeta3

 Kertailen  vihoita ja muistiinpanoistta SMAD- signaalitien jäseniä,  signaalitien  aktivoivaa  reseptoria TGFbeta  ja  siiden proteosomaalista säätöä. Tämä signaalijärjestelmä on   ainakin yhden kerran mainittu  SMAD-sanalla uudessa Cancer kirjassa sivulla 316, joten koetan saada   siitä käsitystä.  Useimmista kehon signaaliteistä ei niin paljon yleisuutista ole, muta tästä heijastuu tauteja ja esim suyöpiä ja jopa perinnöllistätaipumusta syöpiin. Katson mitä siitä uusin Pub;ed sanoo ? 

 

Jollain tavalla pitää olla oelmassa normaali funktio TGFbeta ja SMAD-signaloinnilla.

Yhden ainakin löysin ja sekoskee normaalin rustokudoksen muodostusta.

 https://link.springer.com/article/10.1134/S0006297920040045?fromPaywallRec=true

 

Tässäkin artikkelissa (alla)  ilmeni yhden kerran SMAD  abstraktissa.   Sekä TGFbeta3.

 https://link.springer.com/article/10.1134/S0006297920040045?fromPaywallRec=true  Abstract

Hyaline cartilage is a nonvascular connective tissue covering the joint surface. It consists mostly of the extracellular matrix proteins and a small number of highly differentiated chondrocytes. At present, various techniques for repairing joint surfaces damage, for example, the use of modified cell cultures and biodegradable scaffolds, are under investigation. Molecular mechanisms of cartilage tissue proliferation have been also actively studied in recent years. TGFβ3, which plays a critical role in the proliferation of normal cartilage tissue, is one of the most important protein among cytokines and growth factors affecting chondrogenesis. By interacting directly with receptors on the cell membrane surface, TGFβ3 triggers a cascade of molecular interactions involving transcription factor Sox9. In this review, we describe the effects of TGFβ3 on the receptor complex activation and subsequent intracellular trafficking of Smad proteins and analyze the relation between these processes and upregulation of expression of major extracellular matrix genes, such as col2a1 and acan.

TGFbeta 1  stabiloi SOX9.  

 https://www.oarsijournal.com/article/S1063-4584(16)30318-1/fulltext

 

Tieto TGFbeta3 geenistä GeneCards:

Transforming Growth Factor Beta 3 ^{2 3 5}

Transforming Growth Factor Beta-3 Proprotein ^{3 4}

Prepro-Transforming Growth Factor Beta-3 ^{2 3}

ARVD1 ^{3 5}

ARVD, Arrhythmogenic Right Ventricular Dysplasia 1

• Transforming Growth Factor, Beta 3 ²
• TGF-Beta3 ³
• LDS5 ³
• RNHF ³

https://www.genecards.org/cgi-bin/carddisp.pl?gene=TGFB3&keywords=TGFbeta3 

 This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. This protein is involved in embryogenesis and cell differentiation, and may play a role in wound healing. Mutations in this gene are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1. [provided by RefSeq, Aug 2016]TGFB3 (Transforming Growth Factor Beta 3) is a Protein Coding gene. Diseases associated with TGFB3 include Loeys-Dietz Syndrome 5 and Arrhythmogenic Right Ventricular Dysplasia, Familial, 1. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and MIF Mediated Glucocorticoid Regulation. Gene Ontology (GO) annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is TGFB2.

 

Transforming growth factor beta-3: Multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains remain non-covalently linked rendering TGF-beta-3 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP that control activation of TGF-beta-3 and maintain it in a latent state during storage in extracellular milieus (By similarity). TGF-beta-3 is released from LAP by integrins: integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-beta-3 (By similarity). Once activated following release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity). ( TGFB3_HUMAN,P10600 ) 

Molecular function for TGFB3 Gene according to GENATLAS

Biochemistry:

• transforming growth factor,beta 3,152.6kDa,homodimerizing,expressed by fibroblast,platelet,monocyte,chondrocyte,osteoblasts,including the latency associated peptide (LAP),involved in the pathogenesis of cleft lip and palate TGFB3

LifeMap Function Summary for TGFB3 Gene

During embryonic development, TGFB3 as signaling molecule is secreted from the following cells

• Brain
  • Choroid Plexus Progenitor Cells (Choroid Plexus)
  • Mature Choroid Plexus Cells (Choroid Plexus)
• Cartilage
  • Intervertebral Disc Annulus Fibrosus Cells (Annulus Fibrosus)

It affects the following cells:

• Cartilage
  • Intervertebral Disc Annulus Fibrosus Cells (Annulus Fibrosus)

TGFB3 as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells: See all 5 »

• Cartilage
  • Cartilage Constructs
  • Chondrocyte pellets
  • See all 5 »
• Brain
  • Dopaminergic-like neurons
  • Dorsal forebrain-like neurons
  • Midbrain dopaminergic-like neurons
  • Ventral midbrain dopaminergic-like neurons
  • Ventral/hypothalamic-like neurons