Cortactin in cell migration and cancer at a glance

MacGrath, Stacey M.; Koleske, Anthony J.

doi:10.1242/jcs.093781

Cited by 159 publications

(195 citation statements)

References 100 publications

(139 reference statements)

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“…101 For further readings to cortactin, please see recent reviews. [102][103][104][105] Both WASP and cortactin are targeted and activated by a number of cellular signals. These include the Rho-family GTPases Cdc 42 and Rac, tyrosine kinases, the phosphatidyl (3,4,5) triphosphate, and focal adhesion kinase.…”

Section: The Arp2/3 Complex a Central Player In Junction Dynamics Ofmentioning

confidence: 99%

Dynamics between actin and the VE-cadherin/catenin complex

Taha

Schnittler

2014

Cell Adhesion & Migration

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Section: The Arp2/3 Complex a Central Player In Junction Dynamics Ofmentioning

confidence: 99%

Dynamics between actin and the VE-cadherin/catenin complex

Taha

Schnittler

2014

Cell Adhesion & Migration

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“…The hematopoietic lineage cell-specific protein 1 (HS1, HCLS1) is the homolog of the actin-binding protein cortactin in hematopoietic cells (reviewed in [16]). Structurally, HS1 contains an Nterminal acidic region that binds the Arp2/3 complex.…”

Section: Introductionmentioning

confidence: 99%

“…It was also proposed that Nck directly associates with a proline-rich sequence within CD3ε that becomes accessible upon TCR ligation to more directly link TCR signaling with the actin cytoskeleton [11,12]. In this way, Nck is functionally associated with T-cell activation [13], adhesion [14] and effector function [15].The hematopoietic lineage cell-specific protein 1 (HS1, HCLS1) is the homolog of the actin-binding protein cortactin in hematopoietic cells (reviewed in [16]). Structurally, HS1 contains an Nterminal acidic region that binds the Arp2/3 complex.…”

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SDF1α‐induced interaction of the adapter proteins Nck and HS1 facilitates actin polymerization and migration in T cells

2014

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Noncatalytic region of tyrosine kinase (Nck) is an adapter protein that comprises one SH2 (Src homology) domain and three SH3 domains. Nck links receptors and receptorassociated tyrosine kinases or adapter proteins to proteins that regulate the actin cytoskeleton. Whereas the SH2 domain binds to phosphorylated receptors or associated phosphoproteins, individual interactions of the SH3 domains with proline-based recognition motifs result in the formation of larger protein complexes. In T cells, changes in cell polarity and morphology during T-cell activation and effector function require the T-cell receptor-mediated recruitment and activation of actin-regulatory proteins to initiate cytoskeletal reorganization at the immunological synapse. We previously identified the adapter protein HS1 as a putative Nck-interacting protein. We now demonstrate that the SH2 domain of Nck specifically interacts with HS1 upon phosphorylation of its tyrosine residue 378. We report that in human T cells, ligation of the chemokine receptor CXCR4 by stromal cell-derived factor 1α (SDF1α) induces a rapid and transient phosphorylation of tyrosine 378 of HS1 resulting in an increased association with Nck. Consequently, siRNA-mediated downregulation of HS1 and/or Nck impairs SDF1α-induced actin polymerization and T-cell migration.Keywords: CXCR4 r HS1 r Nck r SDF1α r T cells IntroductionT cells govern adaptive immunity by cytokine secretion or cytotoxic effector function. After development in the thymus, naive T lymphocytes constantly recirculate between the blood stream and lymphoid tissues. At the molecular level, this homing and migration processes rely on complex interactions of selected chemokines with their receptors on respective T cells and of T-cell adhesion molecules binding to their ligands on endothelial cells or the extracellular matrix. Individual interactions elicit specific signaling pathways that induce dynamic cytoskeletal rearrangements, which enable lymphocytes to adhere to or pass a certain substrate or to transmigrate through a given endothelium. Morphologically, circular floating T cells adopt a migratory phenotype characterized Correspondence: Dr. Marcus Lettau e-mail: lettau@immunologie.uni-kiel.de by a leading edge at the front and an uropod at the rear. When T cells encounter their antigen on an antigen-presenting cell in the lymph nodes or spleen, migration is halted and the cells rapidly polarize toward the intercellular contact area. The subsequent formation of the so-called immunological synapse (IS) is again accompanied by complex cytoskeletal changes and comprises the structural basis for T-cell activation. This primary antigenic stimulation ultimately results in cell-cycle progression, clonal expansion, and differentiation to T-effector cells. The activated T cells regain migratory potential, leave the lymphoid tissue, and search the periphery for infected or transformed cells displaying their cognate antigen. Upon antigen encounter, the T cells adhere to their target cell and polarize toward the intercell...

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“…CTN is an important scaffold for promoting the polymerization and rearrangement of the actin cytoskeleton (4). Functionally, CTN, distributed at protrusions and the leading edges, is necessary for cell migration by regulating intercellular adhesion and cell spreading (5). Importantly, CTN is phosphorylated at tyrosine residues in response to growth factor receptors, which regulates cell migration (6).…”

mentioning

confidence: 99%

The Microtubule Plus End Tracking Protein TIP150 Interacts with Cortactin to Steer Directional Cell Migration

Adams

Zhang

Wang

et al. 2016

Journal of Biological Chemistry

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Cell migration is orchestrated by dynamic interactions of microtubules with the plasma membrane cortex. How these interactions facilitate these dynamic processes is still being actively investigated. TIP150 is a newly characterized microtubule plus end tracking protein essential for mitosis and entosis (Ward, T., Wang, M., Liu, X., Wang, Z., Xia, P., Chu, Y., Wang, X., Liu, L., Jiang, K., Yu, H., Yan, M., Wang, J., Hill, D. L., Huang, Y., Zhu, T., and Yao, X. (2013) Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis. J. Biol. Chem. 288, 15771-15785; Xia, P., Zhou, J., Song, X., Wu, B., Liu, X., Li, D., Zhang, S., Wang, Z., Yu, H., Ward, T., Zhang, J., Li, Y., Wang, X., Chen, Y., Guo, Z., and Yao, X. (2014) Aurora A orchestrates entosis by regulating a dynamic MCAK-TIP150 interaction. J. Mol. Cell Biol. 6, 240 -254). Here we show that TIP150 links dynamic microtubules to steer cell migration by interacting with cortactin. Mechanistically, TIP150 binds to cortactin via its C-terminal tail. Interestingly, the C-terminal TIP150 proline-rich region (CT150) binds to the Src homology 3 domain of cortactin specifically, and such an interaction is negatively regulated by EGF-elicited tyrosine phosphorylation of cortactin. Importantly, suppression of TIP150 or overexpression of phospho-mimicking cortactin inhibits polarized cell migration. In addition, CT150 disrupts the biochemical interaction between TIP150 and cortactin in vitro, and perturbation of the TIP150-cortactin interaction in vivo using a membrane-permeable TAT-CT150 peptide results in an inhibition of directional cell migration. We reason that a dynamic TIP150-cortactin interaction orchestrates directional cell migration via coupling dynamic microtubule plus ends to the cortical cytoskeleton.Cell migration is an essential physiological function that is tightly regulated in numerous biological processes, including development, tissue remodeling, wound healing, and tumor metastasis (1, 2). These processes require coordination of dynamic reorganization between the actin filaments and microtubules.Cortactin (CTN) 6 is a multidomain-containing scaffold protein that consists of an N-terminal acidic domain, six and a half tandem repeats, an ␣ helix, a proline-rich region, and an Src Homology (SH3) domain at its C terminus (3). CTN is an important scaffold for promoting the polymerization and rearrangement of the actin cytoskeleton (4). Functionally, CTN, distributed at protrusions and the leading edges, is necessary for cell migration by regulating intercellular adhesion and cell spreading (5). Importantly, CTN is phosphorylated at tyrosine residues in response to growth factor receptors, which regulates cell migration (6).Microtubules, one of the three major components of the cytoskeleton, are required for maintaining the physical and plastic properties of migrating cells (7). The plus en...

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Cortactin in cell migration and cancer at a glance

Cited by 159 publications

References 100 publications

Dynamics between actin and the VE-cadherin/catenin complex

Dynamics between actin and the VE-cadherin/catenin complex

SDF1α‐induced interaction of the adapter proteins Nck and HS1 facilitates actin polymerization and migration in T cells

The Microtubule Plus End Tracking Protein TIP150 Interacts with Cortactin to Steer Directional Cell Migration

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