scholarly journals A novel member of the transmembrane serine/threonine kinase receptor family is specifically expressed in the gonads and in mesenchymal cells adjacent to the mullerian duct

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 189-197 ◽  
Author(s):  
W.M. Baarends ◽  
M.J. van Helmond ◽  
M. Post ◽  
P.J. van der Schoot ◽  
J.W. Hoogerbrugge ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mesenchymal Cells ◽  
Type I ◽  
Mullerian Duct ◽  
Tgf Beta ◽  
Serine Threonine Kinase ◽  
Rnase Protection ◽  
Müllerian Duct ◽  
Threonine Kinase ◽  
Mullerian Ducts

The activin and TGF-beta type II receptors are members of a separate subfamily of transmembrane receptors with intrinsic protein kinase activity, which also includes the recently cloned TGF-beta type I receptor. We have isolated and characterized a cDNA clone (C14) encoding a new member of this subfamily. The domain structure of the C14-encoded protein corresponds with the structure of the other known transmembrane serine/threonine kinase receptors. It also contains the two inserts in the kinase domain that are characteristic for this subfamily. Using in situ hybridization, C14 mRNA was detected in the mesenchymal cells located adjacent to the mullerian ducts of males and females at day 15 (E15) of embryonic development. Marked C14 mRNA expression was also detected in the female gonads. In female E16 embryos, the C14 mRNA expression pattern remained similar to that in E15 embryos. However, in male E16 embryos C14 mRNA was detected in a circular area that includes the degenerating mullerian duct. The expression of C14 mRNA was also studied using RNase protection assays. At E15 and E16, C14 mRNA is expressed in the female as well as in the male urogenital ridge. However, at E19, a high C14 mRNA level in the female urogenital ridge contrasts with a lack of C14 mRNA in the male urogenital ridge. This correlates with the almost complete degeneration of the mullerian ducts in male embryos at E19. C14 mRNA expression was also detected in embryonic testes at E15, E16 and E19 using RNase protection assays, but at much lower levels than those found in the developing ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Mothers against dpp participates in a DDP/TGF-beta responsive serine-threonine kinase signal transduction cascade

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3167-3176 ◽  
Author(s):  
S.J. Newfeld ◽  
A. Mehra ◽  
M.A. Singer ◽  
J.L. Wrana ◽  
L. Attisano ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Nuclear Accumulation ◽  
Target Cells ◽  
Type I ◽  
Dependent Manner ◽  
Tgf Beta ◽  
Serine Threonine Kinase ◽  
Drosophila Cell ◽  
Threonine Kinase ◽  
Signal Transduction Cascade

Mothers against dpp (Mad) is the prototype of a family of genes required for signaling by TGF-beta related ligands. In Drosophila, Mad is specifically required in cells responding to Decapentaplegic (DPP) signals. We further specify the role of Mad in DPP-mediated signaling by utilizing tkvQ199D, an activated form of the DPP type I receptor serine-threonine kinase thick veins (tkv). In the embryonic midgut, tkvQ199D mimics DPP-mediated inductive interactions. Homozygous Mad mutations block signaling by tkvQ199D. Appropriate responses to signaling by tkvQ199D are restored by expression of MAD protein in DPP-target cells. Endogenous MAD is phosphorylated in a ligand-dependent manner in Drosophila cell culture. DPP overexpression in the embryonic midgut induces MAD nuclear accumulation; after withdrawal of the overexpressed DPP signal, MAD is detected only in the cytoplasm. However, in three different tissues and developmental stages actively responding to endogenous DPP, MAD protein is detected in the cytoplasm but not in the nucleus. From these observations, we discuss possible roles for MAD in a DPP-dependent serine-threonine kinase signal transduction cascade integral to the proper interpretation of DPP signals.

scholarly journals Specific deletion of LKB1/Stk11 in the Müllerian duct mesenchyme drives hyperplasia of the periurethral stroma and tumorigenesis in male mice

2017 ◽  
Vol 114 (13) ◽  
pp. 3445-3450 ◽  
Author(s):  
Jitu W. George ◽  
Amanda L. Patterson ◽  
Pradeep S. Tanwar ◽  
André Kajdacsy-Balla ◽  
Gail S. Prins ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Outlet Obstruction ◽  
Prostatic Hyperplasia ◽  
Lineage Tracing ◽  
Urogenital Sinus ◽  
Mullerian Duct ◽  
Serine Threonine Kinase ◽  
Müllerian Duct ◽  
Threonine Kinase ◽  
Conditional Deletion

Nearly all older men will experience lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), the etiology of which is not well understood. We have generated Stk11CKO mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing. The Stk11CKO mice develop prostatic hyperplasia with bladder outlet obstruction, most likely because of stromal expansion. The stromal areas from prostates of Stk11CKO mice, with or without significant expansion, were estrogen receptor positive, which is consistent with both MD mesenchyme-derived cells and the purported importance of estrogen receptors in BPH development and/or progression. In some cases, stromal hyperplasia was admixed with epithelial metaplasia, sometimes with keratin pearls, consistent with squamous cell carcinomas. Mice with conditional deletion of both Stk11 and Pten developed similar features as the Stk11CKO mice, but at a highly accelerated rate, often within the first few months after birth. Western blot analyses showed that the loss of LKB1 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) induces activation of the phospho-5′ adenosine monophosphate-activated protein kinase and phospho-AKT serine/threonine kinase 1 signaling pathways, as well as increased total and active β-catenin. These results suggest that activation of these signaling pathways can induce hyperplasia of the MD stroma, which could play a significant role in the etiology of human BPH.

An activated form of type I serine/threonine kinase receptor TARAM-A reveals a specific signalling pathway involved in fish head organiser formation

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3735-3743 ◽  
Author(s):  
A. Renucci ◽  
V. Lemarchandel ◽  
F. Rosa
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Axis Formation ◽  
Mesoderm Induction ◽  
Type I ◽  
Tgf Beta ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Anterior Dorsal ◽  
Dorsal Mesoderm

The role of Transforming Growth Factor beta (TGF-beta)-related molecules in axis formation and mesoderm patterning in vertebrates has been extensively documented, but the identity and mechanisms of action of the endogenous molecules remained uncertain. In this study, we isolate a novel serine/threonine kinase type I receptor, TARAM-A, expressed during early zebrafish embryogenesis first ubiquitously and then restricted to dorsal mesoderm during gastrulation. A constitutive form of the receptor is able to induce the most anterior dorsal mesoderm rapidly and to confer an anterior organizing activity. By contrast, the wild-type form is only able to induce a local expansion of the dorsal mesoderm. Thus an activated form of TARAM-A is sufficient to induce dorsoanterior structures and TARAM-A may be activated by dorsally localized signals. Our data suggest the existence in fish of a specific TGF-beta-related pathway for anterior dorsal mesoderm induction, possibly mediated by TARAM-A and activated at the late blastula stage by localized dorsal determinant.

Reversible ubiquitination regulates the Smad/TGF-β signalling pathway

2006 ◽  
Vol 34 (5) ◽  
pp. 761-763 ◽  
Author(s):  
S.J. Wicks ◽  
T. Grocott ◽  
K. Haros ◽  
M. Maillard ◽  
P. ten Dijke ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Serine Threonine Kinase ◽  
Full Spectrum ◽  
Threonine Kinase ◽  
Pathological Conditions ◽  
C Terminus ◽  
Β Receptor ◽  
Fine Tune

TGF-β (transforming growth factor-β) signals through serine/threonine kinase receptors and intracellular Smad transcription factors. An important regulatory step involves specific ubiquitination by Smurfs (Smad–ubiquitin regulatory factors), members of the HECT (homologous to E6-associated protein C-terminus) ubiquitin ligase family, which mediate the proteasomal degradation of Smads and/or receptors. Recently, we have defined a novel interaction between Smads and UCH37 (ubiquitin C-terminal hydrolase 37), a DUB (de-ubiquitinating enzyme) that could potentially counteract Smurf-mediated ubiquitination. We have demonstrated specific interactions between UCH37 and inhibitory Smad7, as well as weaker associations with Smad2 and Smad3. Importantly, Smad7 can act as an adaptor able to recruit UCH37 to the type I TGF-β receptor. Consequently, UCH37 dramatically up-regulates TGF-β-dependent gene expression by de-ubiquitinating and stabilizing the type I TGF-β receptor. Our findings suggest that competing effects of ubiquitin ligases and DUBs in complex with Smad7 can serve to fine-tune responses to TGF-βs under various physiological and pathological conditions. Studies are currently under way using activity-based HA (haemagglutinin)-tagged ubiquitin probes to identify the full spectrum of DUBs that impact on Smad/TGF-β signalling activity.

Changes in mRNA expression of MMP-2 in the Müllerian duct of chicken embryo

2004 ◽  
Vol 139 (2) ◽  
pp. 131-136 ◽  
Author(s):  
Yonju Ha ◽  
Akira Tsukada ◽  
Noboru Saito ◽  
Kiyoshi Shimada
Keyword(s):  
Mrna Expression ◽  
Chicken Embryo ◽  
Mullerian Duct ◽  
Müllerian Duct

scholarly journals Bone Morphogenetic Protein Receptor Complexes on the Surface of Live Cells: A New Oligomerization Mode for Serine/Threonine Kinase Receptors

2000 ◽  
Vol 11 (3) ◽  
pp. 1023-1035 ◽  
Author(s):  
Lilach Gilboa ◽  
Anja Nohe ◽  
Tanja Geissendörfer ◽  
Walter Sebald ◽  
Yoav I. Henis ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Live Cells ◽  
Type I ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Receptor Complexes ◽  
Bmp Receptors ◽  
Protein Receptor

The bone morphogenetic proteins (BMPs) play important roles in embryogenesis and normal cell growth. The BMP receptors belong to the family of serine/threonine kinase receptors, whose activation has been investigated intensively for the transforming growth factor-β (TGF-β) receptor subfamily. However, the interactions between the BMP receptors, the composition of the active receptor complex, and the role of the ligand in its formation have not yet been investigated and were usually assumed to follow the same pattern as the TGF-β receptors. Here we demonstrate that the oligomerization pattern of the BMP receptors is different and is more flexible and susceptible to modulation by ligand. Using several complementary approaches, we investigated the formation of homomeric and heteromeric complexes between the two known BMP type I receptors (BR-Ia and BR-Ib) and the BMP type II receptor (BR-II). Coimmunoprecipitation studies detected the formation of heteromeric and homomeric complexes among all the BMP receptor types even in the absence of ligand. These complexes were also detected at the cell surface after BMP-2 binding and cross-linking. Using antibody-mediated immunofluorescence copatching of epitope-tagged receptors, we provide evidence in live cells for preexisting heteromeric (BR-II/BR-Ia and BR-II/BR-Ib) and homomeric (BR-II/BR-II, BR-Ia/ BR-Ia, BR-Ib/ BR-Ib, and also BR-Ia/ BR-Ib) oligomers in the absence of ligand. BMP-2 binding significantly increased hetero- and homo-oligomerization (except for the BR-II homo-oligomer, which binds ligand poorly in the absence of BR-I). In contrast to previous observations on TGF-β receptors, which were found to be fully homodimeric in the absence of ligand, the BMP receptors show a much more flexible oligomerization pattern. This novel feature in the oligomerization mode of the BMP receptors allows higher variety and flexibility in their responses to various ligands as compared with the TGF-β receptors.

scholarly journals Identification of Type I and Type II Serine/Threonine Kinase Receptors for Growth/Differentiation Factor-5

1996 ◽  
Vol 271 (35) ◽  
pp. 21345-21352 ◽  
Author(s):  
Hideki Nishitoh ◽  
Hidenori Ichijo ◽  
Michio Kimura ◽  
Tomoaki Matsumoto ◽  
Fusao Makishima ◽  
...  
Keyword(s):  
Type I ◽  
Type Ii ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 5

scholarly journals Studies on sex-organ development. Oestrogenic effect on ornithine decarboxylase activity in the differentiating Müllerian ducts and other organs of the chick embryo

1978 ◽  
Vol 176 (1) ◽  
pp. 143-149 ◽  
Author(s):  
C S Teng ◽  
C T Teng
Keyword(s):  
Enzyme Activity ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Mullerian Duct ◽  
Stages Of Development ◽  
Müllerian Duct ◽  
Mullerian Ducts ◽  
The Right ◽  
The Brain

The activity of ornithine decarboxylase in the differentiating left and right Müllerian ducts was assayed and compared with that in other embryonic organs, i.e. the liver and the brain throughout the stages of development. In general the enzyme activity was high in the early stages and decreased extensively in the late stages of development. Specifically, in the left and righ Müllerian ducts, the enzyme activity was high from day 8 to day 9 of incubation. In the right duct the enzyme activity started to decline on day 9 and then continuously decreased to an almost undetectable value on day 18 of incubation. In the left duct the enzyme activity also decreased slightly from day 9 to day 12; however, it increased from day 13 to day 15 and finally decreased to a constant value from day 18 until hatching. The alteration in enzyme activity in the Müllerian duct as assayed in vitro during development is not due to the effect of the size of the endogenous ornithine pool. When the enzyme activity was subjected to oestrogen stimulation, an increase of 5–10-fold for the left duct and of 5–3-fold for the right duct was observed during the course of development. No such stimulation was observed with the treatment of progesterone. Testosterone consistently caused a 25–30% inhibition of the enzyme activity in the Müllerian duct. Oestrogen slightly stimulated the enzyme activity in the developing liver but inhibited that of the brain. The concentration of the three polyamines measured in the Müllerian duct corresponds to the activity of the enzyme determined.

Molecular Cloning of a Novel Type I Receptor Serine/Threonine Kinase for the TGFβ Superfamily from Rat Brain

1996 ◽  
Vol 7 (6) ◽  
pp. 467-478 ◽  
Author(s):  
Kunihiro Tsuchida ◽  
Paul E. Sawchenko ◽  
Shin-Ichi Nishikawa ◽  
Wylie W. Vale
Keyword(s):  
Rat Brain ◽  
Molecular Cloning ◽  
Type I ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Tgfβ Superfamily
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