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.

scholarly journals SEL-5, A Serine/Threonine Kinase That Facilitates lin-12 Activity in Caenorhabditis elegans

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1641-1654 ◽  
Author(s):  
Hanna Fares ◽  
Iva Greenwald
Keyword(s):  
Cell Fate ◽  
Point Mutations ◽  
Kinase Domain ◽  
Terminal Region ◽  
Serine Threonine Kinase ◽  
Intracellular Domain ◽  
Cell Fate Decisions ◽  
Threonine Kinase ◽  
Amino Terminal ◽  
Fate Decision

Abstract Ligands present on neighboring cells activate receptors of the LIN-12/Notch family by inducing a proteolytic cleavage event that releases the intracellular domain. Mutations that appear to eliminate sel-5 activity are able to suppress constitutive activity of lin-12(d) mutations that are point mutations in the extracellular domain of LIN-12, but cannot suppress lin-12(intra), the untethered intracellular domain. These results suggest that sel-5 acts prior to or during ligand-dependent release of the intracellular domain. In addition, sel-5 suppression of lin-12(d) mutations is tissue specific: loss of sel-5 activity can suppress defects in the anchor cell/ventral uterine precursor cell fate decision and a sex myoblast/coelomocyte decision, but cannot suppress defects in two different ventral hypodermal cell fate decisions in hermaphrodites and males. sel-5 encodes at least two proteins, from alternatively spliced mRNAs, that share an amino-terminal region and differ in the carboxy-terminal region. The amino-terminal region contains the hallmarks of a serine/threonine kinase domain, which is most similar to mammalian GAK1 and yeast Pak1p.

scholarly journals Rab40/Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration and invasion

2021 ◽  
Author(s):  
Erik S Linklater ◽  
Emily Duncan ◽  
Ke Jun Han ◽  
Algirdas Kaupinis ◽  
Mindaugas Valius ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Stress Fibers ◽  
Actin Dynamics ◽  
Migration And Invasion ◽  
Matrix Remodeling ◽  
Cell Migration And Invasion

Rab40b is a SOCS box containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b/Cullin5 binding decreases cell motility and invasive potential, and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers. We also show that these stress fibers anchor at less dynamic, more stable focal adhesions. Mechanistically, changes in the cytoskeleton and focal adhesion dynamics are mediated in part by EPLIN, which we demonstrate to be a binding partner of Rab40b and a target for Rab40b/Cullin5 dependent localized ubiquitylation and degradation. Thus, we propose a model where the Rab40b/Cullin5 dependent ubiquitylation regulates EPLIN localization to promote cell migration and invasion by altering focal adhesion and cytoskeletal dynamics.

scholarly journals The Drosophila Shark tyrosine kinase is required for embryonic dorsal closure

2000 ◽  
Vol 14 (5) ◽  
pp. 604-614
Author(s):  
Rafael Fernandez ◽  
Fumitaka Takahashi ◽  
Zhao Liu ◽  
Ruth Steward ◽  
David Stein ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Leading Edge ◽  
Dorsal Closure ◽  
Kinase Gene ◽  
Dorsal Midline ◽  
Jnk Signaling ◽  
Amino Terminal ◽  
Tyrosine Kinase Gene ◽  
Epithelial Sheet ◽  
Jnk Signaling Pathway

Dorsal closure (DC) in the Drosophila embryo requires the coordinated interaction of two different functional domains of the epidermal cell layer—the leading edge (LE) and the lateral epidermis. In response to activation of a conserved c-Jun amino-terminal kinase (JNK) signaling module, the dorsal-most layer of cells, which constitute the LE of the stretching epithelial sheet, secrete Dpp, a member of the TGFβ superfamily. Dpp and other LE cell-derived signaling molecules stimulate the bilateral dorsal elongation of cells of the dorsolateral epidermis over the underlaying amnioserosa and the eventual fusion of their LEs along the dorsal midline. We have found that flies bearing a Shark tyrosine kinase gene mutation,shark1, exhibit a DC-defective phenotype. Dpp fails to be expressed in shark1 mutant LE cells. Consistent with these observations, epidermal-specific reconstitution ofshark function or overexpression of an activated form of c-Jun in the shark1 mutant background, rescues the DC defect. Thus, Shark regulates the JNK signaling pathway leading to Dpp expression in LE cells. Furthermore, constitutive activation of the Dpp pathway throughout the epidermis fails to rescue theshark1 DC defect, suggesting that Shark may function in additional pathways in the LE and/or lateral epithelium.

scholarly journals Phosphatidylinositol 4-kinase III beta regulates cell shape, migration, and focal adhesion number

2020 ◽  
Vol 31 (17) ◽  
pp. 1904-1916
Author(s):  
Patricia Bilodeau ◽  
Daniel Jacobsen ◽  
Denise Law-Vinh ◽  
Jonathan M. Lee
Keyword(s):  
Cell Motility ◽  
Focal Adhesion ◽  
Cell Shape ◽  
Leading Edge ◽  
Lipid Kinase ◽  
Fibroblast Migration ◽  
Phosphatidylinositol 4

This work describes a role for the lipid phosphatidylinositol 4-phosphate (PI4P) and lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ) in cell motility, cell shape, and focal adhesion (FA) formation. During fibroblast migration, PI4P vesicles move to the leading edge and fuse with FA there. Deletion of PI4KIIIB impairs fibroblast migration, increases the number of FA, and alters cell shape.

scholarly journals ACK Family Tyrosine Kinase Activity Is a Component of Dcdc42 Signaling during Dorsal Closure in Drosophila melanogaster

2002 ◽  
Vol 22 (11) ◽  
pp. 3685-3697 ◽  
Author(s):  
Kai Ping Sem ◽  
Baharak Zahedi ◽  
Ivan Tan ◽  
Maria Deak ◽  
Louis Lim ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Leading Edge ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Binding Motif ◽  
Dorsal Closure ◽  
Tyrosine Kinase Activity ◽  
Amino Terminal

ABSTRACT We have characterized Drosophila melanogaster ACK (DACK), one of two members of the ACK family of nonreceptor tyrosine kinases in Drosophila. The ACKs are likely effectors for the small GTPase Cdc42, but signaling by these proteins remains poorly defined. ACK family tyrosine kinase activity functions downstream of Drosophila Cdc42 during dorsal closure of the embryo, as overexpression of DACK can rescue the dorsal closure defects caused by dominant-negative Dcdc42. Similar to known participants in dorsal closure, DACK is enriched in the leading edge cells of the advancing epidermis, but it does not signal through activation of the Jun amino-terminal kinase cascade operating in these cells. Transcription of DACK is responsive to changes in Dcdc42 signaling specifically at the leading edge and in the amnioserosa, two tissues involved in dorsal closure. Unlike other members of the ACK family, DACK does not contain a conserved Cdc42-binding motif, and transcriptional regulation may be one route by which Dcdc42 can affect DACK function. Expression of wild-type and kinase-dead DACK transgenes in embryos, and in the developing wing and eye, reveals that ACK family tyrosine kinase activity is involved in a range of developmental events similar to that of Dcdc42.

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 Tropomyosin Isoform Expression Regulates the Transition of Adhesions To Determine Cell Speed and Direction

2009 ◽  
Vol 29 (6) ◽  
pp. 1506-1514 ◽  
Author(s):  
Cuc T. T. Bach ◽  
Sarah Creed ◽  
Jessie Zhong ◽  
Maha Mahmassani ◽  
Galina Schevzov ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Actin Filaments ◽  
Feedback Loop ◽  
Cell Movement ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Mesenchymal Cell ◽  
Critical Determinant ◽  
Focal Complex

ABSTRACT The balance of transition between distinct adhesion types contributes to the regulation of mesenchymal cell migration, and the characteristic association of adhesions with actin filaments led us to question the role of actin filament-associating proteins in the transition between adhesive states. Tropomyosin isoform association with actin filaments imparts distinct filament structures, and we have thus investigated the role for tropomyosins in determining the formation of distinct adhesion structures. Using combinations of overexpression, knockdown, and knockout approaches, we establish that Tm5NM1 preferentially stabilizes focal adhesions and drives the transition to fibrillar adhesions via stabilization of actin filaments. Moreover, our data suggest that the expression of Tm5NM1 is a critical determinant of paxillin phosphorylation, a signaling event that is necessary for focal adhesion disassembly. Thus, we propose that Tm5NM1 can regulate the feedback loop between focal adhesion disassembly and focal complex formation at the leading edge that is required for productive and directed cell movement.

scholarly journals Interaction of monocarboxylate transporter 4 with β1-integrin and its role in cell migration

2009 ◽  
Vol 296 (3) ◽  
pp. C414-C421 ◽  
Author(s):  
Shannon M. Gallagher ◽  
John J. Castorino ◽  
Nancy J. Philp
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Specific Interaction ◽  
Cell Movement ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Monocarboxylate Transporter ◽  
Epithelial Cell Lines

Monocarboxylate transporter (MCT) 4 is a heteromeric proton-coupled lactate transporter that is noncovalently linked to the extracellular matrix metalloproteinase inducer CD147 and is typically expressed in glycolytic tissues. There is increasing evidence to suggest that ion transporters are part of macromolecular complexes involved in regulating β1-integrin adhesion and cell movement. In the present study we examined whether MCTs play a role in cell migration through their interaction with β1-integrin. Using reciprocal coimmunoprecipitation assays, we found that β1-integrin selectively associated with MCT4 in ARPE-19 and MDCK cells, two epithelial cell lines that express both MCT1 and MCT4. In polarized monolayers of ARPE-19 cells, MCT4 and β1-integrin colocalized to the basolateral membrane, while both proteins were found in the leading edge lamellapodia of migrating cells. In scratch-wound assays, MCT4 knockdown slowed migration and increased focal adhesion size. In contrast, silencing MCT1 did not alter the rate of cell migration or focal adhesion size. Taken together, our findings suggest that the specific interaction of MCT4 with β1-integrin may regulate cell migration through modulation of focal adhesions.

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