scholarly journals Neuronal Cell Shape and Neurite Initiation Are Regulated by the Ndr Kinase SAX-1, a Member of the Orb6/COT-1/Warts Serine/Threonine Kinase Family

2000 ◽  
Vol 11 (9) ◽  
pp. 3177-3190 ◽  
Author(s):  
Jennifer A. Zallen ◽  
Erin L. Peckol ◽  
David M. Tobin ◽  
Cornelia I. Bargmann
Keyword(s):  
Cell Shape ◽  
Neuronal Cell ◽  
Neurite Growth ◽  
Dominant Negative ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
C Elegans ◽  
Calcium Calmodulin Dependent ◽  
Binding Domains ◽  
Neurite Initiation

The Caenorhabditis elegans sax-1 gene regulates several aspects of neuronal cell shape. sax-1 mutants have expanded cell bodies and ectopic neurites in many classes of neurons, suggesting that SAX-1 functions to restrict cell and neurite growth. The ectopic neurites in sensory neurons of sax-1mutants resemble the defects caused by decreased sensory activity. However, the activity-dependent pathway, mediated in part by the UNC-43 calcium/calmodulin-dependent kinase II, functions in parallel with SAX-1 to suppress neurite initiation. sax-1 encodes a serine/threonine kinase in the Ndr family that is related to the Orb6 (Schizosaccharomyces pombe), Warts/Lats (Drosophila), and COT-1 (Neurospora) kinases that function in cell shape regulation. These kinases have similarity to Rho kinases but lack consensus Rho-binding domains. Dominant negative mutations in the C. elegans RhoA GTPase cause neuronal cell shape defects similar to those ofsax-1 mutants, and genetic interactions betweenrhoA and sax-1 suggest shared functions. These results suggest that SAX-1/Ndr kinases are endogenous inhibitors of neurite initiation and cell spreading.

scholarly journals A Drosophila homolog of the Rac- and Cdc42-activated serine/threonine kinase PAK is a potential focal adhesion and focal complex protein that colocalizes with dynamic actin structures.

1996 ◽  
Vol 16 (5) ◽  
pp. 1896-1908 ◽  
Author(s):  
N Harden ◽  
J Lee ◽  
H Y Loh ◽  
Y M Ong ◽  
I Tan ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Cell Shape ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Epidermal Cells ◽  
Dorsal Closure ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Amino Terminal ◽  
Drosophila Homolog

Changes in cell morphology are essential in the development of a multicellular organism. The regulation of the cytoskeleton by the Rho subfamily of small GTP-binding proteins is an important determinant of cell shape. The Rho subfamily has been shown to participate in a variety of morphogenetic processes during Drosophila melanogaster development. We describe here a Drosophila homolog, DPAK, of the serine/threonine kinase PAK, a protein which is a target of the Rho subfamily proteins Rac and Cdc42. Rac, Cdc42, and PAK have previously been implicated in signaling by c-Jun amino-terminal kinases. DPAK bound to activated (GTP-bound) Drosophila Rac (DRacA) and Drosophila Cdc42. Similarities in the distributions of DPAK, integrin, and phosphotyrosine suggested an association of DPAK with focal adhesions and Cdc42- and Rac-induced focal adhesion-like focal complexes. DPAK was elevated in the leading edge of epidermal cells, whose morphological changes drive dorsal closure of the embryo. We have previously shown that the accumulation of cytoskeletal elements initiating cell shape changes in these cells could be inhibited by expression of a dominant-negative DRacA transgene. We show that leading-edge epidermal cells flanking segment borders, which express particularly large amounts of DPAK, undergo transient losses of cytoskeletal structures during dorsal closure. We propose that DPAK may be regulating the cytoskeleton through its association with focal adhesions and focal complexes and may be participating with DRacA in a c-Jun amino-terminal kinase signaling pathway recently demonstrated to be required for dorsal closure.

The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1467-1475 ◽  
Author(s):  
J.L. Watts ◽  
D.G. Morton ◽  
J. Bestman ◽  
K.J. Kemphues
Keyword(s):  
Cell Cycle ◽  
Kinase Domain ◽  
Missense Mutations ◽  
Serine Threonine Kinase ◽  
Cell Stage ◽  
Threonine Kinase ◽  
C Elegans ◽  
Human Kinase ◽  
Early Embryos ◽  
Peutz Jeghers Syndrome

During the first cell cycle of Caenorhabditis elegans embryogenesis, asymmetries are established that are essential for determining the subsequent developmental fates of the daughter cells. The maternally expressed par genes are required for establishing this polarity. The products of several of the par genes have been found to be themselves asymmetrically distributed in the first cell cycle. We have identified the par-4 gene of C. elegans, and find that it encodes a putative serine-threonine kinase with similarity to a human kinase associated with Peutz-Jeghers Syndrome, LKB1 (STK11), and a Xenopus egg and embryo kinase, XEEK1. Several strong par-4 mutant alleles are missense mutations that alter conserved residues within the kinase domain, suggesting that kinase activity is essential for PAR-4 function. We find that the PAR-4 protein is present in the gonads, oocytes and early embryos of C. elegans, and is both cytoplasmically and cortically distributed. The cortical distribution begins at the late 1-cell stage, is more pronounced at the 2- and 4-cell stages and is reduced at late stages of embryonic development. We find no asymmetry in the distribution of PAR-4 protein in C. elegans embryos. The distribution of PAR-4 protein in early embryos is unaffected by mutations in the other par genes.

scholarly journals Death-Associated Protein Kinase-Related Protein 1, a Novel Serine/Threonine Kinase Involved in Apoptosis

2000 ◽  
Vol 20 (3) ◽  
pp. 1044-1054 ◽  
Author(s):  
Boaz Inbal ◽  
Gidi Shani ◽  
Ofer Cohen ◽  
Joseph L. Kissil ◽  
Adi Kimchi
Keyword(s):  
Catalytic Domain ◽  
Function Analysis ◽  
Regulatory Region ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Related Protein ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Functional Connections ◽  
Dap Kinase

ABSTRACT In this study we describe the identification and structure-function analysis of a novel death-associated protein (DAP) kinase-related protein, DRP-1. DRP-1 is a 42-kDa Ca2+/calmodulin (CaM)-regulated serine threonine kinase which shows high degree of homology to DAP kinase. The region of homology spans the catalytic domain and the CaM-regulatory region, whereas the remaining C-terminal part of the protein differs completely from DAP kinase and displays no homology to any known protein. The catalytic domain is also homologous to the recently identified ZIP kinase and to a lesser extent to the catalytic domains of DRAK1 and -2. Thus, DAP kinase DRP-1, ZIP kinase, and DRAK1/2 together form a novel subfamily of serine/threonine kinases. DRP-1 is localized to the cytoplasm, as shown by immunostaining and cellular fractionation assays. It binds to CaM, undergoes autophosphorylation, and phosphorylates an exogenous substrate, the myosin light chain, in a Ca2+/CaM-dependent manner. The truncated protein, deleted of the CaM-regulatory domain, was converted into a constitutively active kinase. Ectopically expressed DRP-1 induced apoptosis in various types of cells. Cell killing by DRP-1 was dependent on two features: the status of the catalytic activity, and the presence of the C-terminal 40 amino acids shown to be required for self-dimerization of the kinase. Interestingly, further deletion of the CaM-regulatory region could override the indispensable role of the C-terminal tail in apoptosis and generated a “superkiller” mutant. A dominant negative fragment of DAP kinase encompassing the death domain was found to block apoptosis induced by DRP-1. Conversely, a catalytically inactive mutant of DRP-1, which functioned in a dominant negative manner, was significantly less effective in blocking cell death induced by DAP kinase. Possible functional connections between DAP kinase and DRP-1 are discussed.

scholarly journals A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis

2020 ◽  
Vol 77 (22) ◽  
pp. 4693-4708 ◽  
Author(s):  
Sihyeon An ◽  
Oh Sung Kwon ◽  
Jinbae Yu ◽  
Sung Key Jang
Keyword(s):  
Translational Regulation ◽  
Ectopic Expression ◽  
Translational Repression ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
C Elegans ◽  
Target Sites ◽  
M Phase ◽  
A Subunit ◽  
Cycle Dependent

Abstract During mitosis, translation of most mRNAs is strongly repressed; none of the several explanatory hypotheses suggested can fully explain the molecular basis of this phenomenon. Here we report that cyclin-dependent CDK11/p58—a serine/threonine kinase abundantly expressed during M phase—represses overall translation by phosphorylating a subunit (eIF3F) of the translation factor eIF3 complex that is essential for translation initiation of most mRNAs. Ectopic expression of CDK11/p58 strongly repressed cap-dependent translation, and knockdown of CDK11/p58 nullified the translational repression during M phase. We identified the phosphorylation sites in eIF3F responsible for M phase-specific translational repression by CDK11/p58. Alanine substitutions of CDK11/p58 target sites in eIF3F nullified its effects on cell cycle-dependent translational regulation. The mechanism of translational regulation by the M phase-specific kinase, CDK11/p58, has deep evolutionary roots considering the conservation of CDK11 and its target sites on eIF3F from C. elegans to humans.

The serine/threonine kinase ULK1 is a target of multiple phosphorylation events

2011 ◽  
Vol 440 (2) ◽  
pp. 283-291 ◽  
Author(s):  
Markus Bach ◽  
Mark Larance ◽  
David E. James ◽  
Georg Ramm
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Phosphorylation Site ◽  
Degradation Process ◽  
Dominant Negative ◽  
Serine Threonine Kinase ◽  
Kinase Activation ◽  
Threonine Kinase ◽  
Convergence Point ◽  
Mtor Phosphorylation

Autophagy is a cellular degradation process that is up-regulated upon starvation. Nutrition-dependent regulation of mTOR (mammalian target of rapamycin) is a major determinant of autophagy. RTK (receptor tyrosine kinase) signalling and AMPK (AMP-activated protein kinase) converge upon mTOR to suppress or activate autophagy. Nutrition-dependent regulation of autophagy is mediated via mTOR phosphorylation of the serine/threonine kinase ULK1 (unc51-like kinase 1). In the present study, we also describe ULK1 as an mTOR-independent convergence point for AMPK and RTK signalling. We initially identified ULK1 as a 14-3-3-binding protein and this interaction was enhanced by treatment with AMPK agonists. AMPK interacted with ULK1 and phosphorylated ULK1 at Ser555in vitro. Mutation of this residue to alanine abrogated 14-3-3 binding to ULK1, and in vivo phosphorylation of ULK1 was blocked by a dominant-negative AMPK mutant. We next identified a high-stringency Akt site in ULK1 at Ser774 and showed that phosphorylation at this site was increased by insulin. Finally, we found that the kinase-activation loop of ULK1 contains a consensus phosphorylation site at Thr180 that is required for ULK1 autophosphorylation activity. Collectively, our results suggest that ULK1 may act as a major node for regulation by multiple kinases including AMPK and Akt that play both stimulatory and inhibitory roles in regulating autophagy.

scholarly journals RhoA-Binding Kinase α Translocation Is Facilitated by the Collapse of the Vimentin Intermediate Filament Network

1998 ◽  
Vol 18 (11) ◽  
pp. 6325-6339 ◽  
Author(s):  
Wun-Chey Sin ◽  
Xiang-Qun Chen ◽  
Thomas Leung ◽  
Louis Lim
Keyword(s):  
Structural Integrity ◽  
Morphological Changes ◽  
Dominant Negative ◽  
Cell Periphery ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Complex Process ◽  
Rho Effectors ◽  
Filament Network

ABSTRACT The regulation of morphological changes in eukaryotic cells is a complex process involving major components of the cytoskeleton including actin microfilaments, microtubules, and intermediate filaments (IFs). The putative effector of RhoA, RhoA-binding kinase α (ROKα), is a serine/threonine kinase that has been implicated in the reorganization of actin filaments and in myosin contractility. Here, we show that ROKα also directly affects the structural integrity of IFs. Overexpression of active ROKα, like that of RhoA, caused the collapse of filamentous vimentin, a type III IF. A RhoA-binding-deficient, kinase-inactive ROKα inhibited the collapse of vimentin IFs induced by RhoA in HeLa cells. In vitro, ROKα bound and phosphorylated vimentin at its head-rod domain, thereby inhibiting the assembly of vimentin. ROKα colocalized predominantly with the filamentous vimentin network, which remained intact in serum-starved cells. Treatment of cells with vinblastine, a microtubule-disrupting agent, also resulted in filamentous vimentin collapse and concomitant ROKα translocation to the cell periphery. ROKα translocation did not occur when the vimentin network remained intact in vinblastine-treated cells at 4°C or in the presence of the dominant-negative RhoAN19 mutant. Transient translocation of ROKα was also observed in cells subjected to heat shock, which caused the disassembly of the vimentin network. Thus, the translocation of ROKα to the cell periphery upon overexpression of RhoAV14 or growth factor treatment is associated with disassembly of vimentin IFs. These results indicate that Rho effectors known to act on microfilaments may be involved in regulating the assembly of IFs. Vimentin when phosphorylated also exhibits reduced affinity for the inactive ROKα. The translocation of ROKα from IFs to the cell periphery upon action by activated RhoA and ROKα suggests that ROKα may initiate its own cascade of activation.

scholarly journals Dap-Kinase Participates in TNF-α–And FAS-Induced Apoptosis and Its Function Requires the Death Domain

1999 ◽  
Vol 146 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Ofer Cohen ◽  
Boaz Inbal ◽  
Joseph L. Kissil ◽  
Tal Raveh ◽  
Hanna Berissi ◽  
...  
Keyword(s):  
Cell Death ◽  
Dominant Negative ◽  
Protein Domain ◽  
Dominant Negative Mutant ◽  
Death Domain ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Dap Kinase ◽  
Tnf Α ◽  
Induced Apoptosis

Death-associated protein (DAP)–kinase is a calcium/calmodulin regulated serine/threonine kinase that carries ankyrin repeats, a death domain, and is localized to the cytoskeleton. Here, we report that this kinase is involved in tumor necrosis factor (TNF)-α and Fas-induced apoptosis. Expression of DAP-kinase antisense RNA protected cells from killing by anti–Fas/APO-1 agonistic antibodies. Deletion of the death domain abrogated the apoptotic functions of the kinase, thus, documenting for the first time the importance of this protein domain. Overexpression of a fragment encompassing the death domain of DAP-kinase acted as a specific dominant negative mutant that protected cells from TNF-α, Fas, and FADD/MORT1–induced cell death. DAP-kinase apoptotic function was blocked by bcl-2 as well as by crmA and p35 inhibitors of caspases, but not by the dominant negative mutants of FADD/MORT1 or of caspase 8. Thus, it functions downstream to the receptor complex and upstream to other caspases. The multidomain structure of this serine/threonine kinase, combined with its involvement in cell death induced by several different triggers, place DAP-kinase at one of the central molecular pathways leading to apoptosis.

scholarly journals The Serine/Threonine Kinase Ndr2 Controls Integrin Trafficking and Integrin-Dependent Neurite Growth

2014 ◽  
Vol 34 (15) ◽  
pp. 5342-5354 ◽  
Author(s):  
K. Rehberg ◽  
S. Kliche ◽  
D. A. Madencioglu ◽  
M. Thiere ◽  
B. Muller ◽  
...  
Keyword(s):  
Neurite Growth ◽  
Serine Threonine Kinase ◽  
Threonine Kinase
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