KEY POINTS * Phosphatases can be classified into two families — the tyrosine phosphatases and the serine/threonine phosphatases — that differ in structure, enzymatic mechanism and

regulation. * Phosphatases dephosphorylate proteins on tyrosine, threonine and serine residues to influence protein folding, enzymatic activity and protein–protein interactions. *

Phosphatases affect all components of the migration process including: protrusion of lamellipodia that is induced by remodelling of the actin cytoskeleton and regulated by small GTPase

molecular switches; modulation of the dynamics of matrix-adhesion interaction; actin contraction; rear release; and regulation of migratory directionality. * Phosphatase activity can either

of new technologies for the examination of spatio–temporal regulation of phosphatases, as well as for substrate identification, will provide opportunities to further our understanding of the

role of phosphatases in adhesion and migration. ABSTRACT Many proteins that have been implicated in cell–matrix adhesion and cell migration are phosphorylated, which regulates their

folding, enzymatic activities and protein–protein interactions. Although modulation of cell motility by kinases is well known, increasing evidence confirms that phosphatases are essential at

each stage of the migration process. Phosphatases can control the formation and maintenance of the actin cytoskeleton, regulate small GTPase molecular switches, and modulate the dynamics of

matrix–adhesion interaction, actin contraction, rear release and migratory directionality. Access through your institution Buy or subscribe This is a preview of subscription content, access

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Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PHOSPHOINOSITIDE SIGNALLING IN CELL MOTILITY AND ADHESION

Article 01 April 2025 NON-CATALYTIC ROLE OF PHOSPHOINOSITIDE 3-KINASE IN MESENCHYMAL CELL MIGRATION THROUGH NON-CANONICAL INDUCTION OF P85Β/AP2-MEDIATED ENDOCYTOSIS Article Open access 23

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portion of the extensive work in this field due to length constraints. M.L. is supported by a National Insitutes of Health grant for postdoctoral fellows. M.L.T. is a Scientist of the

Canadian Institutes of Health Research. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and

Craniofacial Research, National Institutes of Health, Building 30/Room 421, 30 Convent Drive, MSC 4370, Bethesda, 20892-4370, Maryland, USA Melinda Larsen & Kenneth M. Yamada * McGill

Cancer Centre and Department of Biochemistry, McGill University, Montreal, H3G 1Y6, Quebec, Canada Michel L. Tremblay Authors * Melinda Larsen View author publications You can also search

for this author inPubMed Google Scholar * Michel L. Tremblay View author publications You can also search for this author inPubMed Google Scholar * Kenneth M. Yamada View author publications

You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Melinda Larsen or Michel L. Tremblay. RELATED LINKS RELATED LINKS DATABASES FLYBASE

Slingshot INTERPRO ADF B′ phosphatases PP PTP SH2 LOCUSLINK LMW-PTP PTEN PTP-PEST SHP2 SWISS-PROT FAK LIMK POPX1 POPX2 PP1 PP2A PTP1B PTPα PTPδ PTPσ PTPφ SHIP SHPS1 FURTHER INFORMATION

Kinases Kinases Migration Phosphatases PPs PPs PTPs PTPs SHIPs GLOSSARY * LAMELLIPODIUM A thin, flat extension at the cell periphery that is filled with a branching meshwork of actin

filaments. * LEADING EDGE The leading, or foremost, region of a motile cell. * FILOPODIA Thin protrusions from cells that are usually supported by microfilaments. * RHO FAMILY OF SMALL

GTPASES A family of monomeric G proteins that comprises isoforms of Rho, Rac and Cdc42. These are important molecular switches and they control cytoskeletal assembly and contraction. *

EXTRACELLULAR MATRIX (ECM). The complex, multi-molecular material that surrounds cells. The ECM comprises a scaffold upon which tissues are organized, it provides cellular microenvironments

and it regulates a variety of cellular functions. * FOCAL COMPLEX A cell–substrate adhesion structure that mediates initial cell adhesion. Formation of the structure is promoted by Rac, and

it can mature to form a focal adhesion. * FOCAL ADHESION A cell-to-substrate adhesion structure that anchors the ends of actin microfilaments (stress fibres) and mediates strong attachment

to substrates. * ACTIN CYTOSKELETON A cytoplasmic structural framework within cells that is composed of F-actin and associated molecules. * INTEGRINS A group of heterodimeric, transmembrane

adhesion receptors for extracellular-matrix proteins such as fibronectin and vitronectin. * STRESS FIBRE Also termed an 'actin microfilament bundle'. A bundle of parallel filaments

that contains F-actin and other contractile molecules, which often stretches between cell attachments as if under stress. * RAFT A discrete detergent-insoluble, glycosphingolipid-,

sphingomyelin- and cholesterol-enriched domain within cellular membranes, where certain signalling lipids and transmembrane proteins that are involved in signalling are thought to be

concentrated. * REACTIVE OXYGEN SPECIES (ROS). Oxygen molecules, containing an unpaired electron in their outermost shell of electrons in an extremely unstable configuration, which quickly

react with another molecule to achieve a stable configuration. * 3D-MATRIX ADHESION A long, thin cell–extracellular-matrix adhesion structure that contains the α5β1 integrin, which is

characteristically formed at cell attachments to 3-dimensional, fibronectin-rich extracellular fibrils. * FIBRILLAR ADHESION An elongated cell–extracellular-matrix adhesion structure that

contains the α5β1 integrin, tensin and fibronectin, and that seems to generate fibronectin fibrils using directed translocation of integrins and cellular contractility. * PODOSOME A circular

cell–substrate adhesion structure that contains integrins and associated proteins such as gelsolin and cortactin, which surround a dense core of actin. * HOLOENZYME An enzyme that consists

of more than one subunit, each usually carrying out a different function and often existing as more than one isoform. * CHEMOTAXIS A type of migration that is stimulated by a gradient of a

chemical stimulant or chemoattractant. * ADHERENS JUNCTIONS Specialized cell–cell adhesions found in epithelium, which contain transmembrane E-cadherin that connects with the cytoskeleton. *

EPITHELIAL–MESENCHYMAL TRANSITION (EMT). A transition of epithelial cells to a migratory phenotype that is more typical of mesenchymal cells. EMT is characterized by loss of adherens

junctions and desmosomes with the acquisition of cell–matrix adhesions, and is necessary at many stages of embryonic development. * AXONAL PATHFINDING The process by which extending nerve

fibres find their way to destinations. * DORSAL CLOSURE A process during _Drosophila_ development in which two epithelial sheets converge, in a coordinated fashion, to close the embryo. *

PRIMITIVE STREAK The site of migration of the mesoderm and definitive endoderm cells from the exterior to the interior of the embryo during gastrulation. It defines the axes of the

developing embryo. * GASTRULATION The process during embryonic development that transforms a blastula into a gastrula and generates the embryonic cell layers: ectoderm, endoderm and

mesoderm. * APICAL ECTODERMAL RIDGE (AER). A region of ectoderm at the distal tip of a limb-bud that is induced by the underlying mesenchyme and is required for sustained outgrowth of the

limb. * SUBSTRATE-TRAPPING MUTANT A phosphatase containing a mutation that allows it to bind to and dephosphorylate a substrate, but not to release it. These are useful tools that allow the

transient association of phosphatases and their substrates to be 'frozen' and so more easily detected. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Larsen, M., Tremblay, M. & Yamada, K. Phosphatases in cell–matrix adhesion and migration. _Nat Rev Mol Cell Biol_ 4, 700–711 (2003). https://doi.org/10.1038/nrm1199 Download

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