Chromosomal localization of three human genes encoding members of the TGF-β superfamily of type I serine/threonine kinase receptors

1998 ◽  
Vol 9 (3) ◽  
pp. 266-268 ◽  
Author(s):  
E. Röijer ◽  
K. Miyazono ◽  
A. -K. Åström ◽  
A. Geurts van Kessel ◽  
P. ten Dijke ◽  
...  
Keyword(s):  
Chromosomal Localization ◽  
Type I ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Human Genes ◽  
Genes Encoding

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.

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

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

scholarly journals Conserved Serine/Threonine Kinase Encoded by CBK1 Regulates Expression of Several Hypha-Associated Transcripts and Genes Encoding Cell Wall Proteins in Candida albicans

2002 ◽  
Vol 184 (7) ◽  
pp. 2058-2061 ◽  
Author(s):  
Mark D. McNemar ◽  
William A. Fonzi
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Morphological Differentiation ◽  
Growth Conditions ◽  
Cell Wall Proteins ◽  
Serine Threonine Kinase ◽  
General Role ◽  
Threonine Kinase ◽  
Genes Encoding ◽  
Opportunistic Fungal Pathogen

ABSTRACT The opportunistic fungal pathogen, Candida albicans, is reported to have several potential virulence factors. A potentially significant factor is the ability to undergo morphological transition from yeast to hypha. This alteration of form is accompanied by many changes within the cell, including alterations in gene expression and cell wall composition. We have isolated a gene that encodes a highly conserved serine/threonine kinase that appears to be involved in the regulation of proteins associated with the cell wall. We have assigned the designation CBK1 (cell wall biosynthesis kinase 1) to this gene. Mutants lacking CBK1 form large aggregates of round cells under all growth conditions and lack the ability to undergo morphological differentiation. Additionally, these mutants show an altered pattern of expression of several transcripts encoding proteins associated with the cell wall. The results suggest that the kinase encoded by CBK1 plays a general role in the maintenance and alteration of the cell wall of C. albicans in all morphologies.

scholarly journals ALK7, a Receptor for Nodal, Is Dispensable for Embryogenesis and Left-Right Patterning in the Mouse

2004 ◽  
Vol 24 (21) ◽  
pp. 9383-9389 ◽  
Author(s):  
Henrik Jörnvall ◽  
Eva Reissmann ◽  
Olov Andersson ◽  
Mehrnaz Mehrkash ◽  
Carlos F. Ibáñez
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Limb Bud ◽  
Mutant Mice ◽  
Type I ◽  
Vertebrate Development ◽  
Serine Threonine Kinase ◽  
Genes Encoding ◽  
Limb Malformations

ABSTRACT Mesendoderm formation and left-right patterning during vertebrate development depend upon selected members of the transforming growth factor β superfamily, particularly Nodal and Nodal-related ligands. Two type I serine/threonine kinase receptors have been identified for Nodal, ALK4 and ALK7. Mouse embryos lacking ALK4 fail to produce mesendoderm and die shortly after gastrulation, resembling the phenotype of Nodal knockout mice. Whether ALK4 contributes to left-right patterning is still unknown. Here we report the generation and initial characterization of mice lacking ALK7. Homozygous mutant mice were born at the expected frequency and remained viable and fertile. Viability at weaning was not different from that of the wild type in ALK7 −/−; Nodal +/− and ALK7 −/−; ALK4 +/− compound mutants. ALK7 and ALK4 were highly expressed in interdigital regions of the developing limb bud. However, ALK7 mutant mice displayed no skeletal abnormalities or limb malformations. None of the left-right patterning abnormalities and organogenesis defects identified in mice carrying mutations in Nodal or in genes encoding ActRIIA and ActRIIB coreceptors, including heart malformations, pulmonary isomerism, right-sided gut, and spleen hypoplasia, were observed in mice lacking ALK7. Finally, the histological organization of the cerebellum, cortex, and hippocampus, all sites of significant ALK7 expression in the rodent brain, appeared normal in ALK7 mutant mice. We conclude that ALK7 is not an essential mediator of Nodal signaling during mesendoderm formation and left-right patterning in the mouse but may instead mediate other activities of Nodal and related ligands in the development or function of particular tissues and organs.

scholarly journals Interaction ofDrosophilaInhibitors of Apoptosis with Thick Veins, a Type I Serine/Threonine Kinase Receptor for Decapentaplegic

1998 ◽  
Vol 273 (16) ◽  
pp. 9353-9356 ◽  
Author(s):  
Eiichi Oeda ◽  
Yoshitomo Oka ◽  
Kohei Miyazono ◽  
Masahiro Kawabata
Keyword(s):  
Type I ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

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 Deletion of the Mycobacterium tuberculosis pknH Gene Confers a Higher Bacillary Load during the Chronic Phase of Infection in BALB/c Mice

2005 ◽  
Vol 187 (16) ◽  
pp. 5751-5760 ◽  
Author(s):  
K. G. Papavinasasundaram ◽  
Bosco Chan ◽  
Ji-Hae Chung ◽  
M. Joseph Colston ◽  
Elaine O. Davis ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Parental Strain ◽  
Chronic Phase ◽  
In Vitro Growth ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Genes Encoding ◽  
Survival Studies ◽  
Mycobacterial Cell Wall

ABSTRACT The role of the serine/threonine kinase PknH in the physiology and virulence of Mycobacterium tuberculosis was assessed by the construction of a pknH deletion mutant. Deletion of the pknH gene did not affect sensitivity to the antimycobacterial drug ethambutol, although it was previously thought to be involved in regulating expression of emb genes encoding arabinosyl transferases, the targets of ethambutol. Nevertheless, transcription analyses revealed that genes associated with mycobacterial cell wall component synthesis, such as emb and ini operons, are downstream substrates of the PknH signaling cascade. In vitro survival studies revealed that a mutant with a deletion of the pknH gene displayed increased resistance to acidified nitrite stress, suggesting that nitric oxide is one of the potential environmental triggers for PknH activation. The effect of pknH deletion on mycobacterial virulence was investigated in BALB/c mice. In this model, the ΔpknH mutant was found to survive and replicate to a higher bacillary load in mouse organs than its parental strain and the pknH-complemented strain. In contrast, another closely related kinase mutant, the ΔpknE mutant, obtained from the same parental strain, was not affected in its virulence phenotype. Infection of THP-1 cells or in vitro growth studies in 7H9 medium did not reveal a significant in vitro growth advantage phenotype for the ΔpknH mutant. In conclusion, we propose that the serine/threonine kinase PknH plays a role in regulating bacillary load in mouse organs to facilitate adaptation to the host environment, possibly by enabling a regulated chronic infection by M. tuberculosis.

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