scholarly journals Regulation of Process Retraction and Cell Migration by EphA3 Is Mediated by the Adaptor Protein Nck1

Biochemistry ◽  
2009 ◽  
Vol 48 (27) ◽  
pp. 6369-6378 ◽  
Author(s):  
Tianjing Hu ◽  
Guanfang Shi ◽  
Louise Larose ◽  
Gonzalo M. Rivera ◽  
Bruce J. Mayer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Adaptor Protein ◽  
Process Retraction

scholarly journals The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration

2016 ◽  
Vol 7 (4) ◽  
pp. e2184-e2184 ◽  
Author(s):  
A E Hall ◽  
W-T Lu ◽  
J D Godfrey ◽  
A V Antonov ◽  
C Paicu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Migration ◽  
Adaptor Protein

scholarly journals CRMP2 as a Candidate Target to Interfere with Lung Cancer Cell Migration

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1533
Author(s):  
Xabier Morales ◽  
Rafael Peláez ◽  
Saray Garasa ◽  
Carlos Ortiz de Solórzano ◽  
Ana Rouzaut
Keyword(s):  
Cell Migration ◽  
Lung Adenocarcinoma ◽  
Cancer Cell ◽  
Adaptor Protein ◽  
Mechanistic Explanation ◽  
In Vitro Assays ◽  
Cancer Cell Migration ◽  
Cortical Actin

Collapsin response mediator protein 2 (CRMP2) is an adaptor protein that adds tubulin dimers to the growing tip of a microtubule. First described in neurons, it is now considered a ubiquitous protein that intervenes in processes such as cytoskeletal remodeling, synaptic connection and trafficking of voltage channels. Mounting evidence supports that CRMP2 plays an essential role in neuropathology and, more recently, in cancer. We have previously described a positive correlation between nuclear phosphorylation of CRMP2 and poor prognosis in lung adenocarcinoma patients. In this work, we studied whether this cytoskeleton molding protein is involved in cancer cell migration. To this aim, we evaluated CRMP2 phosphorylation and localization in the extending lamella of lung adenocarcinoma migrating cells using in vitro assays and in vivo confocal microscopy. We demonstrated that constitutive phosphorylation of CRMP2 impaired lamella formation, cell adhesion and oriented migration. In search of a mechanistic explanation of this phenomenon, we discovered that CRMP2 Ser522 phospho-mimetic mutants display unstable tubulin polymers, unable to bind EB1 plus-Tip protein and the cortical actin adaptor IQGAP1. In addition, integrin recycling is defective and invasive structures are less evident in these mutants. Significantly, mouse xenograft tumors of NSCLC expressing CRMP2 phosphorylation mimetic mutants grew significantly less than wild-type tumors. Given the recent development of small molecule inhibitors of CRMP2 phosphorylation to treat neurodegenerative diseases, our results open the door for their use in cancer treatment.

scholarly journals Crk adaptor proteins mediate actin-dependent T cell migration and mechanosensing induced by the integrin LFA-1

2018 ◽  
Vol 11 (560) ◽  
pp. eaat3178 ◽  
Author(s):  
Nathan H. Roy ◽  
Joanna L. MacKay ◽  
Tanner F. Robertson ◽  
Daniel A. Hammer ◽  
Janis K. Burkhardt
Keyword(s):  
T Cells ◽  
Cell Migration ◽  
T Cell ◽  
Actin Polymerization ◽  
Adaptor Protein ◽  
Leading Edge ◽  
Adaptor Proteins ◽  
Substrate Stiffness ◽  
Lymphocyte Function ◽  
Molecular Events

T cell entry into inflamed tissue involves firm adhesion, spreading, and migration of the T cells across endothelial barriers. These events depend on “outside-in” signals through which engaged integrins direct cytoskeletal reorganization. We investigated the molecular events that mediate this process and found that T cells from mice lacking expression of the adaptor protein Crk exhibited defects in phenotypes induced by the integrin lymphocyte function–associated antigen 1 (LFA-1), namely, actin polymerization, leading edge formation, and two-dimensional cell migration. Crk protein was an essential mediator of LFA-1 signaling–induced phosphorylation of the E3 ubiquitin ligase c-Cbl and its subsequent interaction with the phosphatidylinositol 3-kinase (PI3K) subunit p85, thus promoting PI3K activity and cytoskeletal remodeling. In addition, we found that Crk proteins were required for T cells to respond to changes in substrate stiffness, as measured by alterations in cell spreading and differential phosphorylation of the force-sensitive protein CasL. These findings identify Crk proteins as key intermediates coupling LFA-1 signals to actin remodeling and provide mechanistic insights into how T cells sense and respond to substrate stiffness.

scholarly journals CAS/Crk Coupling Serves as a “Molecular Switch” for Induction of Cell Migration

1998 ◽  
Vol 140 (4) ◽  
pp. 961-972 ◽  
Author(s):  
Richard L. Klemke ◽  
Jie Leng ◽  
Rachel Molander ◽  
Peter C. Brooks ◽  
Kristiina Vuori ◽  
...  
Keyword(s):  
Cell Migration ◽  
Adaptor Protein ◽  
Molecular Switch ◽  
Sh2 Domain ◽  
Carcinoma Cells ◽  
Dominant Negative ◽  
Promote Cell Migration ◽  
Invasive Property

Abstract. Carcinoma cells selected for their ability to migrate in vitro showed enhanced invasive properties in vivo. Associated with this induction of migration was the anchorage-dependent phosphorylation of p130CAS (Crk-associated substrate), leading to its coupling to the adaptor protein c-CrkII (Crk). In fact, expression of CAS or its adaptor protein partner Crk was sufficient to promote cell migration, and this depended on CAS tyrosine phosphorylation facilitating an SH2-mediated complex with Crk. Cytokine-stimulated cell migration was blocked by CAS lacking the Crk binding site or Crk containing a mutant SH2 domain. This migration response was characterized by CAS/Crk localization to membrane ruffles and blocked by the dominant-negative GTPase, Rac, but not Ras. Thus, CAS/Crk assembly serves as a “molecular switch” for the induction of cell migration and appears to contribute to the invasive property of tumors.

scholarly journals Akt Phosphorylation of Serine 21 on Pak1 Modulates Nck Binding and Cell Migration

2003 ◽  
Vol 23 (22) ◽  
pp. 8058-8069 ◽  
Author(s):  
Guo-Lei Zhou ◽  
Ya Zhuo ◽  
Charles C. King ◽  
Benjamin H. Fryer ◽  
Gary M. Bokoch ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinases ◽  
Cellular Proliferation ◽  
Fluorescent Protein ◽  
Focal Adhesions ◽  
Adaptor Protein ◽  
Small Gtpases ◽  
Akt Phosphorylation ◽  
Green Fluorescent

ABSTRACT The p21-activated protein kinases (Paks) regulate cellular proliferation, differentiation, transformation, and survival through multiple downstream signals. Paks are activated directly by the small GTPases Rac and Cdc42 and several protein kinases including Akt and PDK-1. We found that Akt phosphorylated and modestly activated Pak1 in vitro. The major site phosphorylated by Akt on Pak1 mapped to serine 21, a site originally shown to be weakly autophosphorylated on Pak1 when Cdc42 or Rac activates it. A peptide derived from the region surrounding serine 21 was a substrate for Akt but not Pak1 in vitro, and Akt stimulated serine 21 phosphorylation on the full-length Pak1 much better than Rac did. The adaptor protein Nck binds Pak near serine 21, and its association is regulated by phosphorylation of this site. We found that either treatment of Pak1 in vitro with Akt or coexpression of constitutively active Akt with Pak1 reduced Nck binding to Pak1. In HeLa cells, green fluorescent protein-tagged Pak1 was concentrated at focal adhesions and was released when Akt was cotransfected. A peptide containing the Nck binding site of Pak1 fused to a portion of human immunodeficiency virus Tat to allow it to enter cells was used to test the functional importance of Nck/Pak binding in Akt-stimulated cell migration. This Tat-Nck peptide reduced Akt-stimulated cell migration. Together, these data suggest that Akt modulates the association of Pak with Nck to regulate cell migration.

scholarly journals Phosphorylation of Tyrosine Residues 31 and 118 on Paxillin Regulates Cell Migration through an Association with Crk in Nbt-II Cells

2000 ◽  
Vol 148 (5) ◽  
pp. 957-970 ◽  
Author(s):  
Valérie Petit ◽  
Brigitte Boyer ◽  
Delphine Lentz ◽  
Christopher E. Turner ◽  
Jean Paul Thiery ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Critical Role ◽  
Adaptor Protein ◽  
Signaling Molecules ◽  
Sh2 Domain ◽  
Wild Type ◽  
Tyrosine Residues ◽  
Pathological Conditions

Identification of signaling molecules that regulate cell migration is important for understanding fundamental processes in development and the origin of various pathological conditions. The migration of Nara Bladder Tumor II (NBT-II) cells was used to determine which signaling molecules are specifically involved in the collagen-mediated locomotion. We show here that paxillin is tyrosine phosphorylated after induction of motility on collagen. Overexpression of paxillin mutants in which tyrosine 31 and/or tyrosine 118 were replaced by phenylalanine effectively impaired cell motility. Moreover, stimulation of motility by collagen preferentially enhanced the association of paxillin with the SH2 domain of the adaptor protein CrkII. Mutations in both tyrosine 31 and 118 diminished the phosphotyrosine content of paxillin and prevented the formation of the paxillin–Crk complex, suggesting that this association is necessary for collagen-mediated NBT-II cell migration. Other responses to collagen, such as cell adhesion and spreading, were not affected by these mutations. Overexpression of wild-type paxillin or Crk could bypass the migration-deficient phenotype. Both the SH2 and the SH3 domains of CrkII are shown to play a critical role in this collagen-mediated migration. These results demonstrate the important role of the paxillin–Crk complex in the collagen-induced cell motility.

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