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TGF beta

From Wikipedia, the free encyclopedia

The SMAD Pathway
The SMAD Pathway
The DAXX Pathway
The DAXX Pathway

Transforming growth factor beta (TGF-β) is a biological protein that comes in three isoforms called TGF-β1, TGF-β2 and TGF-β3; it was also the original name for the founding member of this family that is now called TGF-β1. The TGF-β family is part of a superfamily of proteins known as the transforming growth factor beta superfamily, which includes inhibins, activin, anti-müllerian hormone, bone morphogenetic protein, decapentaplegic and Vg-1. TGF beta controls proliferation, differentiation, and other functions in most cell types. It can also act as a negative autocrine growth factor.

Contents

[edit] Overview

TGF-β is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. TGF-β acts synergistically with TGFA (MIM 190170) in inducing transformation. It also acts as a negative autocrine growth factor. Dysregulation of TGFB activation and signaling may result in apoptosis. Many cells synthesize TGFB and almost all of them have specific receptors for this peptide.

TGFB1, TGFB2, and TGFB3 all function through the same receptor signaling systems.

[edit] The Structure of TGF-β

The peptide structures of the three members of the TGF-β family are highly similar. They are all encoded as large protein precursors; TGF-β1 contains 390 amino acids and TGF-β2 and TGF-β3 each contain 412 amino acids. They each have an N-terminal signal peptide of 20-30 amino acids that they require for secretion from a cell, a pro-region (called latency associated peptide or LAP), and a 112-114 amino acid C-terminal region that becomes the mature TGF-β molecule following its release from the pro-region by proteolytic cleavage.[1] The mature TGF-β protein dimerizes to produce a 25 KDa active molecule with many conserved structural motifs.[2] TGF-β has nine cysteine residues that are conserved among its family; eight form disulphide bonds within the molecule to create a cysteine knot structure characteristic of the TGF-β superfamily while the ninth cysteine forms a bond with the ninth cysteine of another TGF-β molecule to produce the dimer.[3] Many other conserved residues in TGF-β are thought to form secondary structure through hydrophobic interactions. The region between the fifth and sixth conserved cysteines houses the most divergent area of TGF-β molecules that is exposed at the surface of the molecule and is implicated in receptor binding and specificity of TGF-β.

[edit] Functions

[edit] Role in apoptosis

TGF beta induces apoptosis in numerous cell types. TGF beta can induce apoptosis in two ways: The SMAD pathway or the DAXX pathway.

[edit] SMAD pathway

The SMAD pathway is the classical signaling pathway that TGF beta family members signal through.

In this pathway TGF beta dimers binds to a type II receptor which recruits and phosphorylates a type I receptor.

The type I receptor then recruits and phosphorylates a receptor regulated SMAD (R-SMAD). SMAD3, an R-SMAD, is implicated in inducing apoptosis.

The R-SMAD then binds to the common SMAD (coSMAD) SMAD4 and forms a heteromeric complex. This complex then enters the cell nucleus where it activates the Mitogen-activated protein kinase 8 pathway.

This then triggers apoptosis.

[edit] DAXX pathway

TGF beta may also trigger apoptosis via the death associated protein 6 (DAXX adapter protein).

DAXX has been shown to associate with and bind to the type II TGF beta receptor kinase.

[edit] Role in cell cycle

TGF beta plays a crucial role in the regulation of the cell cycle.

[edit] Types

The primary three are:

  • TGF beta 1 - TGFB1 (OMIM 190180)
  • TGF beta 2 - TGFB2 (OMIM 190220)
  • TGF beta 3 - TGFB3 (OMIM 190230)
  • TGFβ4 precursor was discovered as a gene upregulated during pre-menstrual phase in the endometrail stroma(Kothapalli et al. 1997) and called EBAF (endometrial bleeding associated factor). Later independently discovered to be involved in vertebrate embryonic left right asymmetry determination, and given the name lefty2 (also called Lefty A).

[edit] See also

[edit] External links

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aa - ab - af - ak - als - am - an - ang - ar - arc - as - ast - av - ay - az - ba - bar - bat_smg - bcl - be - be_x_old - bg - bh - bi - bm - bn - bo - bpy - br - bs - bug - bxr - ca - cbk_zam - cdo - ce - ceb - ch - cho - chr - chy - co - cr - crh - cs - csb - cu - cv - cy - da - de - diq - dsb - dv - dz - ee - el - eml - eo - es - et - eu - ext - fa - ff - fi - fiu_vro - fj - fo - fr - frp - fur - fy - ga - gan - gd - gl - glk - gn - got - gu - gv - ha - hak - haw - he - hi - hif - ho - hr - hsb - ht - hu - hy - hz - ia - id - ie - ig - ii - ik - ilo - io - is - it - iu - ja - jbo - jv - ka - kaa - kab - kg - ki - kj - kk - kl - km - kn - ko - kr - ks - ksh - ku - kv - kw - ky - la - lad - lb - lbe - lg - li - lij - lmo - ln - lo - lt - lv - map_bms - mdf - mg - mh - mi - mk - ml - mn - mo - mr - mt - mus - my - myv - mzn - na - nah - nap - nds - nds_nl - ne - new - ng - nl - nn - no - nov - nrm - nv - ny - oc - om - or - os - pa - pag - pam - pap - pdc - pi - pih - pl - pms - ps - pt - qu - quality - rm - rmy - rn - ro - roa_rup - roa_tara - ru - rw - sa - sah - sc - scn - sco - sd - se - sg - sh - si - simple - sk - sl - sm - sn - so - sr - srn - ss - st - stq - su - sv - sw - szl - ta - te - tet - tg - th - ti - tk - tl - tlh - tn - to - tpi - tr - ts - tt - tum - tw - ty - udm - ug - uk - ur - uz - ve - vec - vi - vls - vo - wa - war - wo - wuu - xal - xh - yi - yo - za - zea - zh - zh_classical - zh_min_nan - zh_yue - zu