The TGF-β family and its composite receptors

doi:10.1016/0962-8924(94)90202-X

Trends in Cell Biology

Volume 4, Issue 5, May 1994, Pages 172-178

https://doi.org/10.1016/0962-8924(94)90202-X Get rights and content

Abstract

In their search for regulators of animal growth and development, biologists have often come upon members of the transforming growth factor β(TGF-β) family and have realized that these are among the most versatile carriers of growth and differentiation signals. New evidence suggests that these factors signal through receptors with remarkable structures. Each receptor is a complex of two distantly related transmembrane serine/threonine kinases that are both essential for signalling. TGF-β and related factors have at their disposal a repertoire of such receptors, a feature that could account for their multifunctional nature.

References (60)

N.Q. Mcdonald et al.
Cell
(1993)
A.C. Mcpherron et al.
J. Biol. Chem.
(1993)
G.H. Thomsen et al.
Cell
(1993)
E.L. Ferguson et al.
Cell
(1992)
K. Basler et al.
Cell
(1993)
U. Heberlein et al.
Cell
(1993)
K.M. Lyons et al.
Trends Genet.
(1991)
D.M. Kingsley
Cell
(1992)
J.A. Pietenpol
Cell
(1990)
R.L. Cate
Cell
(1986)

J. Massagué

Cell

(1992)

M. Laiho et al.

J. Biol. Chem.

(1991)

L.S. Mathews et al.

Cell

(1991)

L. Attisano et al.

Cell

(1992)

H.Y. Lin et al.

Cell

(1992)

L.L. Georgi et al.

Cell

(1990)

J.L Wrana

Cell

(1992)

P. Franzén

Cell

(1993)

L. Attisano et al.

Cell

(1993)

M.D. O'Connor-Mccourt et al.

J. Biol. Chem.

(1987)

F. López-Casillas et al.

Cell

(1993)

A. Moustakas et al.

J. Biol. Chem.

(1993)

S. Cheifetz

J. Biol. Chem.

(1992)

A.B. Roberts et al.

J. Massagué

Annu. Rev Cell. Biol.

(1990)

M.P. Schlunegger et al.

Nature

(1992)

S. Daopin et al.

Science

(1992)

W. Vale et al.

R.W. Padgett et al.

K.A. Wharton et al.

Cited by (545)

Investigating structural impact of a valine to isoleucine substitution on anti-Müllerian hormone in silico and genetic association of the variant and AMH expression with egg production in chickens
2020, Journal of Integrative Agriculture
Anti-Müllerian hormone (AMH) acts in maintaining orderly cyclic recruitment of early follicles, suggesting that it is a promising candidate for influencing animal reproductive efficiency. This study aimed to elucidate the effect of a missense mutation of Val566Ile on the structure of AMH protein and the genetic association of Val566Ile and AMH expression with egg production in chickens. Structural perturbations of Val566Ile were predicted by homology modeling. The association of the variant with the number of eggs was tested using a quantitative trait transmission disequilibrium test model. AMH expression in granulosa cells in Lueyang black-boned chickens was compared with that in Nick chickens. The Val⁵⁶⁶ of AMH is a non-conservative amino acid among mammals and birds, but its hydrophobicity is completely conservative. The substitution of Val⁵⁶⁶ for Ile⁵⁶⁶ potentially disrupted hydrogen bonds and solvent accessibility of 22 residues and created a short α-helix in the C terminus of AMH. Despite having striking structure-disrupting potential, the variant was not statistically associated with the number of eggs (P>0.05) in the Lueyang black-boned chickens. We did not detect differential expression of AMH between Lueyang black-boned chickens and Nick chickens (P>0.05). These results confirmed the structural impact of Val566Ile, but suggested that Val566Ile and AMH expression might not be the major genetic determinants for egg production in Lueyang black-boned chickens.
Anti Müllerian Hormone: More than a biomarker of female reproductive function
2019, Journal of Gynecology Obstetrics and Human Reproduction
Anti-Müllerian hormone (AMH), known for its role during sexual differentiation, is a dimeric glycoprotein that belongs to the transforming growth factor-β (TGF-β) family. AMH has recently been identified as a reliable marker of ovarian reserve that can help predict early ovarian follicle loss and menopause onset. AMH levels also reflect the effects of damaging gynecologic surgeries or gonadotoxic treatments such as chemotherapy on ovarian reserve. Furthermore, AMH participates in the diagnosis of certain diseases such as granulosa cell tumors or Polycystic Ovary Syndrome (PCOS). Currently used to establish patient profiles and predict ovarian response to stimulation, its role in ART techniques is crucial. Nevertheless, AMH appears to be a weak independent predictor of qualitative outcomes such as implantation, pregnancy, and live birth. As the reliability and reproducibility of AMH dosage have raised many doubts due to different existing standards and thresholds, an international consensus is still expected to improve AMH measurement and interpretation.
Therapeutic Potential for Bone Morphogenetic Protein 4 in Human Malignant Glioma
2017, Neoplasia (United States)
Citation Excerpt :
Ligand-receptor interaction could be affected by the composition of BMP dimer ligand, whether signaling occurs through the PFC or BISC, and the relative contributions of the two different Type I receptors in mediating downstream activity. For instance, variable signaling through BMPRIA/BMPRII versus BMPRIB/BMPRII complexes occur at different stages in development, affecting unique downstream targets and regulating diverse cellular processes [53,54]. Moreover, a novel non-SMAD protein, PAWS1, associated with SMAD1, may phosphorylate BMPRIA and up-regulate SMAD4 independent target genes, indicating interactions beyond the canonical BMP signaling mechanisms [55].
Human glioma, in particular, malignant forms such as glioblastoma exhibit dismal survival rates despite advances in treatment strategies. A population of glioma cells with stem-like features, glioma cancer stem-like cells (GCSCs), contribute to renewal and maintenance of the tumor cell population and appear responsible for chemotherapeutic and radiation resistance. Bone morphogenetic protein 4 (BMP4), drives differentiation of GCSCs and thus improves therapeutic efficacy. Based on this observation it is imperative that the clinical merits of BMP4 in treating human gliomas should be addressed. This article reviews BMP4 signaling in central nervous system development and in glioma tumorigenesis, and the potential of this molecule as a treatment target in human gliomas. Further work needs to be done to determine if distinct lineages of GCSCs, associated with different glioma sub-classifications, proneural, neural, classical and mesenchymal, differ in responsiveness to BMP4 treatment. Additionally, interaction among BMP4 and cell matrix, tumor-vascular molecules and microglial immune cells also needs to be investigated, as this will enhance our knowledge about the role of BMP4 in human glioma and lead to the identification and/or development of novel therapeutic approaches that improve treatment outcomes of these devastating tumors.
Effect of Low-Intensity Pulsed Ultrasound on a Rat Model of Dentin–Dental Pulp Injury and Repair
2017, Ultrasound in Medicine and Biology
This study investigated histopathologic changes in dental pulp after treatment with low-intensity pulsed ultrasound (LIPUS). Fifty rats were randomly divided into an experimental group (n = 25) and a blank control group (n = 25). In the experimental group, a cavity was prepared in the bilateral maxillary first molars. The upper right first molars were stimulated with LIPUS (30 mW/cm², 1.5 MHz) for 20 min/d. The cavities prepared in the left teeth were used as experimental controls (i.e., no LIPUS). Five rats in each group were sacrificed at days 1, 3, 5, 7 and 14. Inflammatory response was visible at different time points after cavity preparation, peaking at day 3, after which it gradually weakened. More reparative dentin was found on the LIPUS treatment side. transforming growth factor-β1 expression increased after treatment, peaking at day 5 and returning to normal at day 14 on both sides, but was stronger with LIPUS treatment. SMAD2 and SMAD3 expressions in the dental pulp gradually increased after cavity preparation, especially in the experimental group. LIPUS promoted the repair of dentin–pulp complex injury, to a certain extent and should be investigated further as a potential therapy.
Bone morphogenetic protein signaling: the pathway and its regulation
2024, Genetics
Secondary glaucoma: Toward interventions based on molecular underpinnings
2024, WIREs Mechanisms of Disease

View all citing articles on Scopus

View full text

Trends in Cell Biology

ReviewThe TGF-β family and its composite receptors

Abstract

Cell

J. Biol. Chem.

Cell

Cell

Cell

Cell

Trends Genet.

Cell

Cell

Cell

Cell

J. Biol. Chem.

Cell

Cell

Cell

Cell

Cell

Cell

Cell

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Biol. Chem.

Annu. Rev Cell. Biol.

Nature

Science

Review
The TGF-β family and its composite receptors