Affinage

Showing DOCK1 — DOCK180 is a alias.

DOCK1

Dedicator of cytokinesis protein 1 · UniProt Q14185

Length
1865 aa
Mass
215.3 kDa
Annotated
2026-06-09
100 papers in source corpus 51 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DOCK1 (DOCK180) is an atypical, Rac1-specific guanine nucleotide exchange factor that converts upstream receptor and lipid signals into localized Rac1 activation to drive cytoskeletal remodeling during apoptotic-cell engulfment, directional migration, myoblast fusion, axon guidance, and cardiovascular development (PMID:9808620, PMID:9548255, PMID:12134158). Its catalytic DHR-2 (Docker/CZH2) domain directly recognizes nucleotide-free Rac1 and is both necessary and sufficient to catalyze GTP loading, defining DOCK1 and its relatives as a conserved superfamily of unconventional GEFs distinct from Dbl-family proteins (PMID:12134158, PMID:12432077). DOCK1 functions as a bipartite GEF with ELMO: ELMO binding relieves an autoinhibitory intramolecular contact between the N-terminal SH3 domain and DHR-2, stabilizes the nucleotide-free Rac transition state through its PH domain in trans, and protects DOCK1 from ubiquitin-dependent degradation at the membrane (PMID:12134158, PMID:15247908, PMID:15723800, PMID:16495483). Membrane targeting of the GEF is governed by the DHR-1 domain, which adopts a C2 fold that binds PtdIns(3,4,5)P3 to couple PI3K signaling to Rac activation at the leading edge, and by a C-terminal polybasic cluster that binds phosphatidic acid to drive dorsal ruffle formation (PMID:16025104, PMID:20167601, PMID:23362269). Upstream, DOCK1 is engaged by integrin/p130Cas/CrkII complexes and engulfment receptors including αvβ5 and BAI1 during clearance of apoptotic cells, and by RhoG-loaded ELMO, the netrin receptor DCC, and chemokine and growth-factor receptors (CXCR4, HER2, PDGFRα, MET/AXL) to direct migration and development (PMID:9733740, PMID:11146654, PMID:12879077, PMID:17960134, PMID:18066058, PMID:20829512, PMID:23592719). Src- and PKA-dependent phosphorylation at Y722, Y1811, and S1250 tunes DOCK1 activity downstream of oncogenic receptors, and DOCK1-driven Rac1 activation supports macropinocytic nutrient uptake, invasion, and metastasis, making it a tractable target via the selective inhibitor TBOPP (PMID:22080864, PMID:22323579, PMID:23728337, PMID:28467910, PMID:29432733). Beyond canonical GEF signaling, DOCK1 also has a Rac1-independent role in retrograde endosome-to-TGN trafficking through DHR-1-mediated binding to sorting nexins (PMID:18596235).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 Medium

    Established that DOCK180 is a membrane-translocating CRK-binding protein whose relocation to the plasma membrane is required to alter cell morphology, the first hint of a signaling effector role.

    Evidence Molecular cloning and farnesylation membrane-targeting construct with morphological readout in 3T3 cells

    PMID:8657152

    Open questions at the time
    • No molecular activity assigned
    • Rac connection not yet made
    • Endogenous regulation of membrane targeting unknown
  2. 1998 High

    Defined DOCK180 as a specific activator of Rac1 acting within integrin/p130Cas/CrkII signaling, answering what GTPase the protein controls and in what receptor context.

    Evidence GTP-Rac pulldowns, dominant-negative Rac1 epistasis, and reciprocal co-IP in 293T/NIH 3T3 cells, plus genetic conservation in C. elegans (CED-5) and Drosophila (MBC)

    PMID:9548255 PMID:9733740 PMID:9808620 PMID:9808621

    Open questions at the time
    • Catalytic mechanism of Rac activation not yet defined
    • Whether binding alone vs enzymatic activity drives GTP loading unresolved
  3. 2000 High

    Showed that an engulfment receptor (αvβ5 integrin) recruits the p130Cas–CrkII–DOCK180 complex to trigger Rac1-dependent phagosome formation, linking the GEF to apoptotic-cell clearance.

    Evidence Co-IP, Rac1-GTP pulldown, β5 cytoplasmic-tail mutants, and phagocytosis assays

    PMID:11146654

    Open questions at the time
    • Direct PS-recognition receptor not yet identified
    • Mechanism coupling integrin engagement to GEF activation unclear
  4. 2001 High

    Identified ELMO/CED-12 as an obligate partner forming a conserved CrkII–DOCK180–ELMO–Rac module, and localized DOCK180 membrane recruitment to PtdIns(3,4,5)P3 binding, defining the core signaling complex and its lipid input.

    Evidence Yeast two-hybrid, co-IP, C. elegans genetic rescue/epistasis, PtdIns(3,4,5)P3 bead pulldown with PI3K co-expression

    PMID:11171081 PMID:11240126 PMID:11369773 PMID:11595183 PMID:11703940

    Open questions at the time
    • Biochemical role of ELMO in catalysis not defined
    • Lipid-binding domain not yet mapped at residue level
  5. 2002 High

    Demonstrated that the DHR-2/Docker domain directly binds nucleotide-free Rac and catalyzes GTP loading, with ELMO augmenting exchange, establishing DOCK180–ELMO as an unconventional bipartite Rac-GEF and founding a new GEF superfamily.

    Evidence In vitro nucleotide exchange assays, domain mapping, trimeric ELMO1–Dock180–Rac1 complex detection, cell-based Rac-GTP pulldown

    PMID:12134158 PMID:12432077

    Open questions at the time
    • Structural basis of Rac recognition not yet solved
    • How upstream signals gate catalysis unresolved
  6. 2003 High

    Placed RhoG upstream of ELMO–DOCK180 as a GTP-dependent activator and showed that complex localization to lamellipodia, not bulk Rac activation, drives migration, refining how and where the GEF acts.

    Evidence GTP-dependent co-IP, constitutively active/dominant-negative RhoG, domain-deletion migration assays, C. elegans rescue, neurite-outgrowth and spreading assays

    PMID:12879077 PMID:14638695

    Open questions at the time
    • How RhoG–ELMO engagement is triggered by receptors unclear
    • Spatial coupling of localization to catalysis not mechanistically resolved
  7. 2004 High

    Resolved ELMO's catalytic contribution by showing its PH domain stabilizes Rac in the nucleotide-free transition state in trans, and reported a large nuclear DOCK180/ELMO complex with retained GEF activity.

    Evidence In vitro GEF assays with ELMO PH-domain mutagenesis, phagocytosis/migration assays, C. elegans rescue, biochemical fractionation and gel filtration

    PMID:15247908 PMID:15288806

    Open questions at the time
    • Functional significance of nuclear complex not established
    • MFG-E8/PSR upstream coupling not fully reconstituted
  8. 2005 High

    Defined the autoinhibition mechanism—intramolecular SH3–DHR-2 contact blocks Rac access, relieved by ELMO—and showed the DHR-1 domain couples PI3K/PtdIns(3,4,5)P3 to directional Rac activation, separating GEF activity from spatial control.

    Evidence Intramolecular binding competition, in vitro/in vivo lipid binding, DHR-1 domain-swap rescue, directional migration assays, ARF6/ARNO epistasis with catalytic-dead and ELMO-coupling mutants

    PMID:15700267 PMID:15723800 PMID:16025104 PMID:16213822

    Open questions at the time
    • Structural detail of DHR-1–lipid recognition not yet solved
    • Quantitative contribution of autoinhibition release vs ELMO stabilization unresolved
  9. 2007 High

    Expanded the upstream receptor repertoire by identifying BAI1 as a PS-binding engulfment GPCR forming a BAI1–ELMO–DOCK180 complex, and DCC as a netrin receptor linking DOCK180 to axon guidance in vivo.

    Evidence Trimeric complex co-IP, PS-binding assays, in vitro/in vivo phagocytosis, Rac1-GTP pulldown, in vivo chick commissural axon guidance with knockdown

    PMID:17960134 PMID:18066058

    Open questions at the time
    • How distinct receptors converge on the same GEF in different cell types unresolved
    • Receptor-to-GEF activation step not biochemically reconstituted
  10. 2008 High

    Resolved the ELMO1–DOCK180 binding interface structurally and uncovered a Rac1-independent role for DHR-1 in retrograde endosome-to-TGN trafficking via sorting nexins, broadening DOCK180's functional scope.

    Evidence X-ray structure of ELMO1 PH domain with mutagenesis and co-IP; mass spectrometry-identified SNX5 interaction with knockdown and CI-MPR trafficking/domain-rescue readouts; ANKRD28 competition experiments

    PMID:18596235 PMID:18768751 PMID:19118547

    Open questions at the time
    • Physiological importance of the trafficking role relative to GEF function unclear
    • How competing SH3 partners are selected in vivo unresolved
  11. 2010 High

    Provided the structural basis for membrane targeting by showing DHR-1 is a C2-fold domain with a basic pocket for the PtdIns(3,4,5)P3 head group, and established DOCK180 as essential for cardiovascular development downstream of CXCR4 in vivo.

    Evidence X-ray crystal structure of DHR-1 with point mutagenesis and cell polarization assays; targeted SH3-domain deletion in mice with cardiovascular phenotyping and CXCL12-induced Rac assays

    PMID:20016009 PMID:20167601 PMID:20829512 PMID:21900250

    Open questions at the time
    • How lipid binding and GEF catalysis are allosterically coupled unresolved
    • Cell-type-specific receptor inputs in vivo not dissected
  12. 2013 High

    Established phosphorylation-based and lipid-based control of DOCK1 in oncogenic signaling—Src-dependent Y1811, PKA-dependent S1250, and PA binding—and demonstrated DOCK1 requirement for HER2-driven and CXCR4-driven tumor growth and metastasis in vivo.

    Evidence Phospho-specific antibodies, site-specific mutant rescue (Y1811F, S1250L), in vitro PKA kinase assay, PA lipid-binding assay with DOCK1/DOCK5 knockout MEFs, conditional DOCK1 knockout HER2 mouse model, Gαi2–ELMO1 co-IP with in vivo metastasis

    PMID:22080864 PMID:23362269 PMID:23441967 PMID:23591873 PMID:23592719 PMID:23728337

    Open questions at the time
    • Integration of multiple phosphosites into a unified activation logic unresolved
    • Whether phosphorylation alters catalysis vs localization vs partner binding not fully separated
  13. 2012 High

    Identified Src-family-dependent Y722 phosphorylation downstream of EGFRvIII and an EGFR–DOCK180–RAC1–MLK3–JNK axis as drivers of glioblastoma invasion, linking receptor tyrosine kinase oncogenes to a defined DOCK1 signaling output.

    Evidence Phospho-specific antibody, SFK inhibitors, shRNA depletion, Y722F mutant, JNK activation, migration/invasion assays

    PMID:22323579 PMID:28487380

    Open questions at the time
    • Relative contribution of Y722 vs Y1811 vs S1250 in tumors unresolved
    • Downstream effector selectivity of Rac1 not defined
  14. 2017 High

    Demonstrated that DOCK1 GEF activity is required for macropinocytosis-dependent nutrient uptake and invasion in Ras- and Rac1P29S-transformed cells, and validated the selective inhibitor TBOPP as suppressing metastasis without affecting DOCK2/DOCK5.

    Evidence Genetic DOCK1 inactivation in MEFs, chemical screen for TBOPP with DOCK family selectivity controls, in vitro nucleotide exchange on Rac1P29S, macropinocytosis/invasion assays, in vivo mouse metastasis models

    PMID:25118935 PMID:28467910 PMID:29432733

    Open questions at the time
    • Mechanism coupling Rac1 activation to macropinosome formation not detailed
    • TBOPP mode of GEF inhibition not structurally defined
  15. 2022 High

    Identified DOCK1-mediated RAC1 activation as a metformin-resistance mechanism, showing phosphorylation-driven DOCK1 activity promotes survival and that TBOPP potentiates anti-tumor activity across organoid and mouse models.

    Evidence Genome-wide CRISPR-Cas9 knockout screen, phosphorylation and Rac1-GTP assays, TBOPP treatment in cell lines, patient-derived organoids, and xenograft/immunocompetent mouse models

    PMID:35217990

    Open questions at the time
    • Kinase responsible for metformin-induced DOCK1 phosphorylation not identified
    • Downstream survival effectors of Rac1 not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple inputs—ELMO autoinhibition release, DHR-1/PA lipid binding, RhoG/G-protein/receptor engagement, and Src/PKA phosphorylation—are integrated into a single quantitative activation logic at defined membrane microdomains remains unresolved.
  • No unified structural model of the activated receptor–DOCK1–ELMO–Rac assembly
  • Physiological role of the nuclear DOCK180/ELMO complex unknown
  • How phosphosite combinations tune catalysis vs localization not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-5653656 Vesicle-mediated transport 1
Partners
BCAR1CRKDCCELMO1ERBB2RAC1RHOGSNX5
Complex memberships
BAI1-ELMO-DOCK180 engulfment complexDOCK1-ELMO bipartite Rac-GEF complexMET-AXL-ELMO2-DOCK180 complexp130Cas-CrkII-DOCK180 complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 DOCK180 was cloned as a 180 kDa CRK SH3-binding protein; when artificially membrane-targeted via a farnesylation signal, it localized to the cytoplasmic membrane and changed cell morphology from spindle to flat polygonal, indicating that membrane translocation of DOCK180 is required for its morphological effects. Molecular cloning, farnesylation membrane-targeting construct, morphological assay in 3T3 cells Molecular and cellular biology Medium 8657152
1998 DOCK180 directly binds Rac1 (but not RhoA or Cdc42Hs), overexpression increases GTP-bound Rac1 in cells, and coexpression of CrkII and p130Cas enhances DOCK180-dependent Rac1 activation; dominant-negative Rac1 suppresses DOCK180-induced membrane spreading, establishing DOCK180 as a novel activator of Rac1 in integrin signaling. GTP-Rac1 pulldown assay, overexpression, dominant-negative Rac1, JNK activation assay in 293T cells Genes & development High 9808620
1998 CED-5, the C. elegans ortholog of DOCK180, is required for engulfment of cell corpses and cell migration of distal tip cells; human DOCK180 expression in C. elegans rescues the cell-migration defect of ced-5 mutants, establishing functional conservation of the CDM family in surface extension during engulfment. C. elegans genetics, transgenic rescue with human DOCK180, phenotypic analysis Nature High 9548255
1998 DOCK180 is phosphorylated and associates with CrkII specifically upon integrin stimulation or v-src/v-crk transformation; DOCK180 expression induces hyperphosphorylation of p130Cas and increased CrkII–p130Cas complex formation; coexpression of p130Cas and CrkII with DOCK180 induces focal-adhesion-localized membrane spreading, placing DOCK180 as an upregulator of the CrkII–p130Cas integrin signaling complex. Co-immunoprecipitation, reconstitution in NIH 3T3 and 3Y1 cells, phosphorylation assays, integrin stimulation The Journal of biological chemistry High 9733740
1998 Drosophila Myoblast City (MBC), the DOCK180 homolog, is required for Rac-specific signaling in dorsal closure, myogenesis, and neural development; mammalian DOCK180 associates with Rac but not Cdc42 in a nucleotide-independent manner, establishing Mbc/DOCK180 as a specific upstream regulator of Rac. Drosophila mutant screen, genetic analysis, co-immunoprecipitation with Rac and Cdc42 Genes & development High 9808621
2000 The αvβ5 integrin recruits the p130Cas–CrkII–DOCK180 molecular complex upon engagement with apoptotic cells, triggering Rac1 activation and phagosome formation; signaling through the β5 cytoplasmic tail is required for internalization, establishing DOCK180 as the effector linking αvβ5 integrin to Rac1 activation during phagocytosis. Co-immunoprecipitation, Rac1-GTP pulldown, dominant-negative constructs, β5 cytoplasmic tail mutants, phagocytosis assays Nature cell biology High 11146654
2001 DOCK180 binds to PtdIns(3,4,5)P3 through a C-terminal basic region; PI3K activation translocates DOCK180 to the plasma membrane without necessarily increasing GTP-Rac in the absence of membrane targeting, indicating PtdIns(3,4,5)P3 controls DOCK180 membrane recruitment. PtdIns(3,4,5)P3-APB bead pulldown, PI3K co-expression, GTP-Rac assays, deletion mutant analysis The Biochemical journal Medium 11171081
2001 CED-12/ELMO directly binds to CED-5/DOCK180 and forms a ternary complex with CED-2/CrkII; this evolutionarily conserved CED-12–CED-5 complex acts as an upstream activator of Rac1, and ELMO1 functionally cooperates with CrkII and Dock180 to promote phagocytosis and cell shape changes. Yeast two-hybrid, co-immunoprecipitation, C. elegans genetic rescue, phagocytosis assay in mammalian cells Cell High 11595183
2001 DOCK180 promotes Rac activation through the CED-2/CrkII–CED-5/DOCK180–CED-12/ELMO–CED-10/Rac pathway; CED-12 forms a ternary complex with CED-2 and CED-5 in vitro and its membrane localization is proposed to activate CED-10/Rac leading to cytoskeletal reorganization during cell migration and engulfment. In vitro protein binding assays, C. elegans genetics, epistasis analysis, cell migration and phagocytosis assays Developmental cell High 11703940
2001 Laminin-10/11 preferentially activates Rac (not Rho) via the p130Cas–CrkII–DOCK180 pathway; phosphorylation of p130Cas and increased formation of the p130Cas–CrkII–DOCK180 complex is associated with Rac activation, and CrkII mutants defective in DOCK180 binding suppress cell migration on laminin-10/11. GTP-Rac/Rho pulldown, co-immunoprecipitation, dominant-negative CrkII mutants, Transwell migration assay The Journal of biological chemistry Medium 11369773
2002 A conserved domain within Dock180 (the Docker/DHR-2/CZH2 domain) specifically recognizes nucleotide-free Rac and mediates GTP loading of Rac in vitro; ELMO1 is required for efficient GTP loading in cells, augments the Dock180–Rac interaction, and a trimeric ELMO1–Dock180–Rac1 complex can be detected, establishing the Dock180–ELMO complex as an unconventional bipartite GEF for Rac. In vitro nucleotide exchange assay, co-immunoprecipitation, domain mapping, cell-based Rac-GTP pulldown Nature cell biology High 12134158
2002 The DHR-2 domain of DOCK180 specifically binds nucleotide-free Rac and activates Rac in vitro and in vivo; DHR-2 is both necessary and sufficient for Rac activation; several DOCK180-related proteins possess DHR-2 domains with GEF activity toward Rac or Cdc42, defining an evolutionarily conserved superfamily of atypical GEFs. In vitro nucleotide exchange assay, domain deletion/reconstitution, cell-based Rac-GTP assay Journal of cell science High 12432077
2003 The Dock180–ELMO1 complex, which activates Rac, is required for mammalian cell migration; the Dock180–ELMO1 complex must form and localize to lamellipodia (via ELMO1 N-terminal 330 aa) for migration, not merely general Rac activation; CED-5/Dock180 function in migration in C. elegans also requires complex formation and Rac activation. Transwell migration assay, domain deletion mutants, C. elegans transgenic rescue, lamellipodia localization by immunofluorescence The Journal of biological chemistry High 14638695
2003 RhoG directly interacts with ELMO in a GTP-dependent manner and forms a ternary complex with Dock180, leading to Rac1 activation; the RhoG–Elmo–Dock180 pathway is required for integrin-mediated Rac1 activation, cell spreading, and NGF-induced neurite outgrowth. Co-immunoprecipitation, GTP-dependent binding assay, dominant-negative and constitutively active RhoG, cell spreading and neurite outgrowth assays Nature High 12879077
2003 C. elegans PSR-1 (phosphatidylserine receptor) acts in the same engulfment pathway as CED-5/DOCK180 and CED-12/ELMO, possibly through direct interaction with CED-5 and CED-12, placing the phosphatidylserine receptor upstream of the CED-2–CED-5–CED-10–CED-12 signaling pathway. C. elegans genetics, in vitro binding assay (PSR-1 binding to PS), epistasis analysis Science Medium 14645848
2004 The PH domain of ELMO binds the Dock180–Rac complex in trans, stabilizing Rac in the nucleotide-free transition state; this PH-domain-dependent mechanism is essential for phagocytosis and cell migration both in mammalian cells and in C. elegans. In vitro GEF assay, mutagenesis of ELMO PH domain, phagocytosis and migration assays, C. elegans genetic rescue Nature structural & molecular biology High 15247908
2004 MFG-E8 acts as a ligand for αvβ5 integrin, and coexpression of MFG-E8 with αvβ5 integrin potentiates integrin-mediated Rac1 activation; antisense DOCK180 abrogates MFG-E8–αvβ5-mediated Rac activation and impairs phagocytosis of apoptotic cells, establishing DOCK180 as the essential GEF downstream of the MFG-E8–αvβ5 signaling module. Rac1-GTP pulldown, antisense DOCK180 knockdown, mutagenesis of MFG-E8 RGD motif, phagocytosis assay Experimental cell research Medium 14697347
2005 The DHR-1 domain of DOCK180 binds PtdIns(3,4,5)P3 in vitro and in vivo and localizes the DOCK180 signaling complex to PtdIns(3,4,5)P3-rich regions at the leading edge; a form of DOCK180 lacking DHR-1 fails to promote cell migration despite inducing Rac GTP-loading, and replacement of DHR-1 with a canonical PH domain restores full function, demonstrating that DHR-1 couples PI3K signaling to Rac activation for directional cell movement. Lipid-binding assay (in vitro and in vivo), domain-swap experiments, cell migration assay, live-cell imaging of PtdIns(3,4,5)P3 localization Nature cell biology High 16025104
2005 At basal state, the N-terminal SH3 domain of Dock180 intramolecularly binds its own Docker/DHR-2 domain, sterically blocking Rac access; ELMO binding to the SH3 domain disrupts this SH3–Docker interaction, relieving steric inhibition and contributing to Rac GEF activity (steric-inhibition model for Dock180 family regulation). Domain interaction mapping, in vitro binding competition, cell-based Rac-GTP assay, C. elegans genetic rescue Current biology High 15723800
2005 ARNO-dependent ARF6 activation promotes Rac1 activation through the Dock180/Elmo bipartite GEF complex; catalytically inactive Dock180 and an Elmo mutant unable to couple to Dock180 both block ARNO-induced Rac activation and cell motility, while a similar β-PIX mutant does not, establishing Dock180/Elmo as the specific downstream effector linking ARF6 to Rac activation at the leading edge. Catalytic-dead Dock180 mutant, Elmo coupling mutant, Rac1-GTP pulldown, cell motility assay in MDCK cells, immunolocalization Current biology High 16213822
2005 The C-terminal SH3 domain of CrkII regulates the stability and turnover of the DOCK180/ELMO Rac-GEF complex; a W276K CrkII mutation constitutively tethers the Crk/DOCK180/ELMO complex (with RhoG) and increases Rac-GTP loading, whereas the N-terminal SH3 promotes assembly between CrkII and DOCK180. Co-immunoprecipitation, Rac-GTP pulldown, phagocytosis assay, domain mutagenesis of CrkII Journal of cellular physiology Medium 15700267
2006 Shigella effector IpgB1 mimics RhoG to bind ELMO and exploit the RhoG–ELMO–Dock180 pathway, stimulating Rac1 activity and membrane ruffles; ELMO and Dock180 knockdown cells show reduced Shigella invasiveness and IpgB1-induced ruffles, demonstrating that pathogens can hijack the ELMO–Dock180 Rac-GEF module for cell invasion. Pulldown identifying ELMO as IpgB1 binding partner, siRNA knockdown of ELMO and Dock180, Rac1 activity assay, bacterial invasion assay, immunolocalization Nature cell biology High 17173036
2006 Elmo1 inhibits ubiquitylation of Dock180 on the plasma membrane, thereby preventing proteasomal degradation of Dock180; the Dock180 protein is constitutively ubiquitylated and its levels are enhanced by proteasome inhibitor; EGF, Crk, and adhesion signals enhance Dock180 ubiquitylation, while Elmo1 counteracts this, providing a mechanism for local control of Rac activation. In vivo ubiquitylation assay, proteasome inhibitor treatment, co-expression experiments, immunofluorescence, membrane fractionation Journal of cell science Medium 16495483
2007 BAI1, a seven-transmembrane adhesion-GPCR, functions as an upstream engulfment receptor that directly binds phosphatidylserine on apoptotic cells via its thrombospondin type 1 repeats; BAI1 forms a trimeric complex with ELMO and Dock180, and cooperates with the ELMO/Dock180/Rac pathway to promote maximal engulfment of apoptotic cells. Co-immunoprecipitation of BAI1–ELMO–Dock180 complex, phosphatidylserine binding assay, knockdown/overexpression phagocytosis assay ex vivo and in vivo Nature High 17960134
2007 DOCK180 interacts with the netrin receptor DCC; netrin stimulation promotes formation of a DOCK180–DCC complex, leading to Rac1 activation; knockdown of DOCK180 reduces netrin-induced Rac1 activation, axon outgrowth, and axon attraction in vertebrate neurons; in vivo, DOCK180 is required for commissural axon projection in the neural tube. Co-immunoprecipitation, Rac1-GTP pulldown, siRNA knockdown, axon guidance and outgrowth assays, in vivo chick spinal cord experiments Nature neuroscience High 18066058
2007 In zebrafish, Dock1 and the closely related Dock5 are both required for embryonic fast-twitch myoblast fusion; the adaptor proteins Crk and Crkl, which physically interact with Dock proteins, are also required for myoblast fusion, placing Dock1 downstream of Crk/Crkl in the vertebrate myoblast fusion pathway. Morpholino antisense knockdown in zebrafish, phenotypic analysis of myoblast fusion Development Medium 17670792
2008 The DHR-1 domain of DOCK180 binds to SNX5 (and SNX1/2/6) at endosomes; DOCK180 colocalizes with SNX5 at endosomes; knockdown of SNX5 or DOCK180 (but not Rac1) causes redistribution of the cation-independent mannose 6-phosphate receptor (CI-MPR) from TGN to endosomes; DHR-1 expression alone restores CI-MPR distribution in DOCK180 knockdown cells, revealing a Rac1-GEF-independent role for DOCK180 in retrograde endosome-to-TGN trafficking. Mass spectrometry (nanoLC-MS/MS) to identify binding partners, co-immunoprecipitation of SNX5, siRNA knockdown, immunofluorescence of CI-MPR localization, domain-rescue experiment Molecular biology of the cell High 18596235
2008 ANKRD28 interacts with DOCK180 via its SH3 domain in an ELMO-competing manner; ANKRD28 knockdown reduces cell migration velocity and alters focal adhesion protein distribution; coexpression of ANKRD28 with p130Cas, Crk, and DOCK180 induces p130Cas hyperphosphorylation and multiple long cellular processes, while ELMO coexpression instead produces broad lamellipodia, demonstrating that competing SH3-domain partners specify distinct outputs of the DOCK180–Rac pathway. Co-immunoprecipitation, siRNA knockdown, migration velocity assay, immunofluorescence of focal adhesion proteins, morphological analysis Experimental cell research Medium 19118547
2008 The alpha-helical extension of the ELMO1 PH domain (N-terminal amphipathic helix) directly mediates interaction with DOCK180; the ELMO1 PH domain structurally resembles FERM domains and cannot bind phospholipids; disruption of both DOCK180-interaction sites on ELMO1 (N-terminal helix and proline-rich/SH3 interaction) is required to fully disrupt the complex; loss of ELMO–DOCK180 coupling impairs Rac signaling without affecting DOCK180 GEF activity per se, implying additional roles for ELMO in Rac signal output. X-ray crystal structure of ELMO1 PH domain, mutagenesis of hydrophobic helix residues, co-immunoprecipitation, Rac signaling assays Molecular biology of the cell High 18768751
2009 uPAR cooperates with β3 integrin-containing complexes to drive formation of the p130Cas–CrkII signaling complex, leading to DOCK180-dependent Rac activation, elongated-mesenchymal morphology, and cell motility/invasion; DOCK180 is identified as the specific GEF acting downstream of uPAR. Co-immunoprecipitation, Rac1-GTP pulldown, siRNA knockdown of DOCK180, morphology and invasion assays The Journal of cell biology Medium 18725541
2009 GRASP/Tamalin and IPCEF scaffold proteins promote assembly of an ARNO–Dock180 multiprotein complex via the ARNO coiled-coil domain; knockdown of either GRASP or IPCEF prevents the ARNO–Dock180 association and ARNO-induced Rac1 activation and motility, showing that these scaffolds are required for ARF-to-Rac GTPase crosstalk. Co-immunoprecipitation, Rac1-GTP pulldown, siRNA knockdown, cell motility assay Molecular biology of the cell Medium 20016009
2010 The DHR-1 domain of Dock1 adopts a C2 domain scaffold with surface loops that form a basic pocket recognizing the PtdIns(3,4,5)P3 head group; point mutations that abolish phospholipid binding in vitro also abolish Dock1-induced cell polarization, establishing the structural basis for membrane targeting of Dock1's GEF activity. X-ray crystal structure of DHR-1, phospholipid binding assay, point mutagenesis, cell polarization assay The Journal of biological chemistry High 20167601
2010 Targeted deletion of the SH3 domain of DOCK180 in mice leads to embryonic lethality with markedly reduced DOCK180 protein expression; DOCK180-deficient mice exhibit cardiovascular abnormalities resembling CXCR4-deficient mice; in DOCK180-knockdown endothelial cells, CXCL12-induced Rac activation and cell motility are impaired, establishing DOCK180 as a link between CXCR4 signaling and Rac activation controlling cardiovascular development. Targeted gene deletion in mice, Rac-GTP pulldown in knockdown cells, cell motility assay, cardiovascular phenotyping Circulation research High 20829512
2011 PDGFRα signaling leads to Src-dependent phosphorylation of Dock180 at tyrosine 1811 (Dock180(Y1811)), enhancing association with CrkII and p130Cas and activating Rac1 to promote glioma cell growth, survival, and invasion; Dock180(Y1811F) mutant abrogates PDGFRα-stimulated activities, establishing Y1811 phosphorylation as the mechanistic link between PDGFRα and Rac1 activation. Phospho-specific antibody, siRNA knockdown with RNAi-resistant rescue (WT vs Y1811F), co-immunoprecipitation, Rac1-GTP pulldown, in vivo glioma tumor assays The Journal of clinical investigation High 22080864
2011 The RhoG–ELMO1–Dock180 signaling module is required for dendritic spine morphogenesis in hippocampal neurons; depletion of Dock180 inhibits spine formation while overexpression promotes it; ELMO1 functions in complex with Dock180 to activate Rac GTPase for spine morphogenesis; RhoG acts upstream of the ELMO1–Dock180 complex in this context. RNAi screen of 70 Rho-GEFs, shRNA knockdown of Dock180, overexpression, Rac-GTP pulldown, confocal imaging of spine morphology The Journal of biological chemistry Medium 21900250
2012 EGFRvIII promotes glioblastoma tumorigenesis through Src family kinase (SFK)-dependent phosphorylation of Dock180 at tyrosine 722 (Dock180(Y722)), stimulating Rac1 signaling, cell survival, and migration; pharmacological or shRNA inhibition of SFKs attenuates EGFRvIII-induced Dock180(Y722) phosphorylation and Rac1 activity; Dock180(Y722F) mutant inhibits EGFRvIII-stimulated activities. Phospho-specific antibody, SFK pharmacological inhibitors, shRNA depletion, Y722F mutant, Rac1-GTP pulldown, migration and survival assays Proceedings of the National Academy of Sciences High 22323579
2013 EGFRvIII induces PKA-dependent serine phosphorylation of Dock180 at S1250 within its DHR-2 domain; PKA inhibitors block this phosphorylation; expression of Dock180(S1250L) but not wild-type Dock180 in EGFRvIII-expressing glioma cells inhibits proliferation, survival, migration in vitro and tumor growth/invasion in vivo. In vitro PKA kinase assay, PKA inhibitors (H-89, KT5720), PKA inhibitor peptide overexpression, S1250L mutant rescue assays, Rac1-GTP pulldown, in vivo intracranial tumor model Oncogene High 23728337
2013 DOCK1 interacts with HER2 and promotes HER2-induced Rac1 activation and cell migration; mammary-gland-specific inactivation of DOCK1 in a HER2 breast cancer mouse model significantly decreases tumor growth and lung metastasis; DOCK1 is required for maximal activation of HER2 effectors c-JUN and STAT3. Co-immunoprecipitation (DOCK1–HER2), Rac1-GTP pulldown, conditional DOCK1 knockout mouse model (HER2 background), tumor growth and metastasis quantification, gene expression profiling Proceedings of the National Academy of Sciences High 23592719
2013 CXCL12 stimulation promotes interaction between Gαi2 and ELMO1; Gαi2-dependent membrane translocation of ELMO1 associates with Dock180 to activate Rac1 and Rac2; both Gi signaling and ELMO1 are required for CXCL12-mediated actin polymerization and migration of breast cancer cells; knockdown of ELMO1 impairs lung metastasis in vivo. Co-immunoprecipitation (Gαi2–ELMO1), Rac1/2-GTP pulldown, siRNA knockdown, actin polymerization assay, migration/invasion assay, in vivo metastasis model Nature communications High 23591873
2013 DOCK1 is recruited to dorsal ruffles via binding of its C-terminal polybasic amino acid cluster to phosphatidic acid (PA); DOCK5 does not bind PA and is dispensable for dorsal ruffle formation; blocking PA–DOCK1 interaction impairs PDGF-induced dorsal ruffle formation; phospholipase D, which synthesizes PA, is specifically required for dorsal (not peripheral) ruffle formation, establishing a phospholipase D–PA–DOCK1 axis for dorsal ruffle biogenesis. PA lipid-binding assay, DOCK1/DOCK5 deficient MEFs, PDGF stimulation, membrane ruffle imaging, PLD inhibition The Journal of biological chemistry High 23362269
2013 GRASP/Tamalin directly binds both cytohesin-2/ARNO (via its coiled-coil domain) and Dock180 (via the Ala/Pro-rich region of GRASP interacting with the SH3 domain of Dock180); GRASP knockdown impairs HGF-stimulated Rac1 activation and epithelial migration, showing GRASP bridges the ARF-GEF and Rac-GEF to coordinate GTPase crosstalk. Direct binding assay (pull-down), siRNA knockdown, Rac1-GTP pulldown, migration assay BMC cell biology Medium 23441967
2014 Dock1 and Rac1 are required for efficient engulfment of apoptotic cells by mammary epithelial phagocytes; conditional inactivation of Dock1 or Rac1 in the mammary gland delays initiation and progression of involution and impairs Stat3 activation, revealing an unexpected role for Dock1/Rac1 signaling in initiating mammary gland involution via Stat3. Conditional knockout mouse models (mammary-gland-specific Dock1 and Rac1 deletion), in vitro phagocytosis assay, immunohistochemistry, Stat3 activation western blot Cell death & disease High 25118935
2015 ELMO1/Dock180 protects endothelial cells from apoptosis via activation of the Rac1–PAK–AKT signaling cascade; overexpression of Elmo1 and Dock180 in zebrafish reduces apoptotic EC number and promotes blood vessel formation during embryogenesis. Overexpression and knockdown in human ECs, caspase-3/7 and annexin V apoptosis assays, Rac1/PAK/AKT activation western blots, in vivo zebrafish vascular development The Journal of biological chemistry Medium 25586182
2017 Genetic inactivation of DOCK1 ablates macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells; TBOPP, a selective DOCK1 inhibitor that blocks GEF function, suppresses DOCK1-mediated invasion and macropinocytosis without impairing the closely related DOCK2 and DOCK5; TBOPP suppresses cancer metastasis and growth in vivo. Genetic DOCK1 inactivation (MEFs), chemical library screen identifying TBOPP, selectivity assays against DOCK2/DOCK5, macropinocytosis and invasion assays, in vivo mouse metastasis and tumor growth models Cell reports High 28467910
2017 DOCK180 activates the MLK3–JNK signaling axis in a RAC1-dependent manner downstream of EGFR; MLK3 silencing or MLK inhibition blocks EGF-induced JNK activation and GBM cell migration/invasion; DOCK180 overexpression in invasive GBM cells drives invasion through the EGFR–DOCK180–RAC1–MLK3–JNK pathway. siRNA knockdown of MLK3 and DOCK180, MLK pharmacological inhibitor, JNK activation assay, migration and invasion assays Molecular cancer research Medium 28487380
2018 HGF induces formation of a MET–AXL–ELMO2–DOCK180 complex on the plasma membrane, stimulating RAC1-dependent cytoskeleton reorganization, cell migration, and invasion; both MET and AXL kinase activities are required for RAC1 activation through this complex. Co-immunoprecipitation (MET–AXL–ELMO2–DOCK180), RAC1-GTP pulldown, kinase inhibition, siRNA knockdown, migration/invasion assay, live-cell imaging The Journal of biological chemistry Medium 30108175
2018 The catalytic DHR-2 domain of DOCK1 greatly accelerates GDP/GTP exchange of Rac1P29S (a self-activating melanoma mutation); in DOCK1-deficient MEFs, Rac1P29S fails to induce matrix invasion and macropinocytosis that are seen in wild-type MEFs; selective DOCK1 inhibitor suppresses invasion and macropinocytosis in melanoma and breast cancer cells harboring Rac1P29S. In vitro nucleotide exchange assay (DOCK1 DHR-2 + Rac1P29S), DOCK1-deficient MEFs, selective DOCK1 inhibitor (TBOPP), invasion and macropinocytosis assays in cancer cells Biochemical and biophysical research communications High 29432733
2018 Mutations in zebrafish dock1 result in delayed radial sorting and decreased myelination of peripheral axons by Schwann cells, without affecting Schwann cell number or migration, demonstrating that Dock1 GEF activity is required for Schwann cell cytoskeletal rearrangements during myelination. Forward genetic screen in zebrafish, morpholino rescue/complementation, in situ hybridization, transmission electron microscopy, live imaging Neural development Medium 30089513
2022 Metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, contributing to metformin resistance; the selective DOCK1 inhibitor TBOPP potentiates metformin's anti-tumor activity in liver cancer cell lines, patient-derived organoids, and in vivo xenograft and immunocompetent mouse models, establishing DOCK1-mediated RAC1 activation as a resistance mechanism to metformin. Genome-wide CRISPR-Cas9 knockout screen, phosphorylation assays, Rac1-GTP pulldown, TBOPP pharmacological inhibition, in vitro and in vivo tumor models, patient-derived organoids Protein & cell High 35217990
2004 Endogenous DOCK180 exists as a large (~700 kDa) nuclear complex with ELMO proteins; this nuclear DOCK180/ELMO complex retains functional Rac-GEF activity; DOCK180 associates with different ELMO isoforms (ELMO1, 2, or 3) in different cell lines, suggesting cell-type-specific nuclear complexes. Biochemical fractionation, gel filtration chromatography, co-immunoprecipitation, in vitro Rac-GEF assay of nuclear fractions Archives of biochemistry and biophysics Medium 15288806
2001 Nck-2 adaptor protein interacts with DOCK180 via its second and third SH3 domains binding to the C-terminal region of DOCK180 (residues 1819–1836 as primary site); tandem SH3 domains enhance weak individual interactions, with KD values of ~415 nM and ~3 nM for the two binding events as measured by surface plasmon resonance. Yeast two-hybrid screen, surface plasmon resonance kinetic analysis, SH3 domain point mutagenesis, deletion mapping FEBS letters Medium 11240126

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 676 17960134
2002 Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nature cell biology 482 12134158
2001 CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 472 11595183
1998 Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes & development 377 9808620
2002 Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. Journal of cell science 342 12432077
2000 alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells. Nature cell biology 317 11146654
1998 C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 315 9548255
2003 RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature 291 12879077
1996 DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Molecular and cellular biology 290 8657152
2007 GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. Trends in cell biology 269 17765544
2003 Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. The Journal of biological chemistry 194 14638695
2005 A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling. Nature cell biology 188 16025104
2004 The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells. Experimental cell research 181 14697347
1998 Evidence that DOCK180 up-regulates signals from the CrkII-p130(Cas) complex. The Journal of biological chemistry 179 9733740
1998 Myoblast city, the Drosophila homolog of DOCK180/CED-5, is required in a Rac signaling pathway utilized for multiple developmental processes. Genes & development 178 9808621
2003 Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science (New York, N.Y.) 164 14645848
2001 Laminin-10/11 and fibronectin differentially regulate integrin-dependent Rho and Rac activation via p130(Cas)-CrkII-DOCK180 pathway. The Journal of biological chemistry 143 11369773
2001 C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment. Developmental cell 136 11703940
2005 The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1. Current biology : CB 130 16213822
2006 Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery. Nature cell biology 122 17173036
2007 A role for the Myoblast city homologues Dock1 and Dock5 and the adaptor proteins Crk and Crk-like in zebrafish myoblast fusion. Development (Cambridge, England) 117 17670792
2007 ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion. Cancer research 116 17671188
2013 Association between Gαi2 and ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis. Nature communications 112 23591873
2004 PH domain of ELMO functions in trans to regulate Rac activation via Dock180. Nature structural & molecular biology 110 15247908
2011 Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans. The Journal of clinical investigation 101 22080864
2008 uPAR promotes formation of the p130Cas-Crk complex to activate Rac through DOCK180. The Journal of cell biology 95 18725541
2012 miR-124-regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1 and Cdc42 signalling. The EMBO journal 93 22588079
2005 A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs. Current biology : CB 93 15723800
2007 Netrin signal transduction and the guanine nucleotide exchange factor DOCK180 in attractive signaling. Nature neuroscience 92 18066058
2004 Isolation and characterisation of DOCK8, a member of the DOCK180-related regulators of cell morphology. FEBS letters 91 15304341
2013 Rac-specific guanine nucleotide exchange factor DOCK1 is a critical regulator of HER2-mediated breast cancer metastasis. Proceedings of the National Academy of Sciences of the United States of America 90 23592719
2004 Activation of Rac1 by paxillin-Crk-DOCK180 signaling complex is antagonized by Rap1 in migrating NBT-II cells. The Journal of biological chemistry 85 15308668
2008 An alpha-helical extension of the ELMO1 pleckstrin homology domain mediates direct interaction to DOCK180 and is critical in Rac signaling. Molecular biology of the cell 83 18768751
2011 Major host factors involved in epithelial cell invasion of Campylobacter jejuni: role of fibronectin, integrin beta1, FAK, Tiam-1, and DOCK180 in activating Rho GTPase Rac1. Frontiers in cellular and infection microbiology 74 22919583
2019 Circular RNA DOCK1 promotes bladder carcinoma progression via modulating circDOCK1/hsa-miR-132-3p/Sox5 signalling pathway. Cell proliferation 71 30983072
2006 Dock180-ELMO cooperation in Rac activation. Methods in enzymology 68 16472672
1998 Development of highly selective SH3 binding peptides for Crk and CRKL which disrupt Crk-complexes with DOCK180, SoS and C3G. Oncogene 68 9591773
2013 EGFRvIII stimulates glioma growth and invasion through PKA-dependent serine phosphorylation of Dock180. Oncogene 65 23728337
2012 Phosphorylation of dedicator of cytokinesis 1 (Dock180) at tyrosine residue Y722 by Src family kinases mediates EGFRvIII-driven glioblastoma tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 62 22323579
2010 Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs). The Journal of biological chemistry 58 20167601
2017 Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1. Cell reports 56 28467910
2006 Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42. The Journal of biological chemistry 51 16968698
2001 Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3. The Biochemical journal 50 11171081
2006 Lysyl oxidase regulates actin filament formation through the p130(Cas)/Crk/DOCK180 signaling complex. Journal of cellular biochemistry 48 16440329
2010 DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4. Circulation research 46 20829512
2007 Identification of two signaling submodules within the CrkII/ELMO/Dock180 pathway regulating engulfment of apoptotic cells. Cell death and differentiation 46 17304244
2011 The RhoG/ELMO1/Dock180 signaling module is required for spine morphogenesis in hippocampal neurons. The Journal of biological chemistry 44 21900250
2011 Opening up on ELMO regulation: New insights into the control of Rac signaling by the DOCK180/ELMO complex. Small GTPases 44 22292130
2013 Phosphatidic acid-dependent recruitment and function of the Rac activator DOCK1 during dorsal ruffle formation. The Journal of biological chemistry 42 23362269
2009 GRASP and IPCEF promote ARF-to-Rac signaling and cell migration by coordinating the association of ARNO/cytohesin 2 with Dock180. Molecular biology of the cell 42 20016009
2019 MiR-486-5p inhibits IL-22-induced epithelial-mesenchymal transition of breast cancer cell by repressing Dock1. Journal of Cancer 41 31528235
2018 Annexin A5 regulates hepatocarcinoma malignancy via CRKI/II-DOCK180-RAC1 integrin and MEK-ERK pathways. Cell death & disease 41 29802377
2005 C-terminal SH3 domain of CrkII regulates the assembly and function of the DOCK180/ELMO Rac-GEF. Journal of cellular physiology 41 15700267
2022 Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer. Protein & cell 40 35217990
2001 Identification and kinetic analysis of the interaction between Nck-2 and DOCK180. FEBS letters 39 11240126
2020 Circular RNA DOCK1 downregulates microRNA-124 to induce the growth of human thyroid cancer cell lines. BioFactors (Oxford, England) 36 32584497
2006 Elmo1 inhibits ubiquitylation of Dock180. Journal of cell science 34 16495483
2009 The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 20237902
2018 HGF-induced formation of the MET-AXL-ELMO2-DOCK180 complex promotes RAC1 activation, receptor clustering, and cancer cell migration and invasion. The Journal of biological chemistry 30 30108175
2008 The DHR1 domain of DOCK180 binds to SNX5 and regulates cation-independent mannose 6-phosphate receptor transport. Molecular biology of the cell 29 18596235
2017 EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion. Molecular cancer research : MCR 28 28487380
2014 Impaired cell death and mammary gland involution in the absence of Dock1 and Rac1 signaling. Cell death & disease 28 25118935
2011 The β1-integrin-p-FAK-p130Cas-DOCK180-RhoA-vinculin is a novel regulatory protein complex at the apical ectoplasmic specialization in adult rat testes. Spermatogenesis 28 21866278
2015 The bipartite rac1 Guanine nucleotide exchange factor engulfment and cell motility 1/dedicator of cytokinesis 180 (elmo1/dock180) protects endothelial cells from apoptosis in blood vessel development. The Journal of biological chemistry 27 25586182
2008 Ankyrin repeat domain 28 (ANKRD28), a novel binding partner of DOCK180, promotes cell migration by regulating focal adhesion formation. Experimental cell research 27 19118547
2021 Circ_DOCK1 regulates USP11 through miR-132-3p to control colorectal cancer progression. World journal of surgical oncology 26 33685455
2018 Downregulation of Dock1 and Elmo1 suppresses the migration and invasion of triple-negative breast cancer epithelial cells through the RhoA/Rac1 pathway. Oncology letters 24 30127952
2008 DOCK5 and DOCK1 regulate Caco-2 intestinal epithelial cell spreading and migration on collagen IV. The Journal of biological chemistry 24 19004829
2014 Enoxaparin sensitizes human non-small-cell lung carcinomas to gefitinib by inhibiting DOCK1 expression, vimentin phosphorylation, and Akt activation. Molecular pharmacology 23 25488183
2021 CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells. Frontiers in cell and developmental biology 22 34109173
2008 Mutation of Dock5, a member of the guanine exchange factor Dock180 superfamily, in the rupture of lens cataract mouse. Experimental eye research 22 18396277
2019 DOCK1 Regulates Growth and Motility through the RRP1B-Claudin-1 Pathway in Claudin-Low Breast Cancer Cells. Cancers 21 31717460
2018 DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29S mutation. Biochemical and biophysical research communications 21 29432733
2016 Dock1 promotes the mesenchymal transition of glioma and is modulated by MiR-31. Neuropathology and applied neurobiology 21 26946516
2008 Dictyostelium Dock180-related RacGEFs regulate the actin cytoskeleton during cell motility. Molecular biology of the cell 21 19037099
2014 Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 20 24819662
2022 Actin Up: An Overview of the Rac GEF Dock1/Dock180 and Its Role in Cytoskeleton Rearrangement. Cells 19 36428994
2016 PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway. Scientific reports 18 27052191
2004 Nuclear localization of the DOCK180/ELMO complex. Archives of biochemistry and biophysics 18 15288806
2021 LINC00665 promotes the progression of acute myeloid leukemia by regulating the miR-4458/DOCK1 pathway. Scientific reports 17 33658535
2014 Protein kinase A-dependent phosphorylation of Dock180 at serine residue 1250 is important for glioma growth and invasion stimulated by platelet derived-growth factor receptor α. Neuro-oncology 17 25468898
2013 The scaffolding protein GRASP/Tamalin directly binds to Dock180 as well as to cytohesins facilitating GTPase crosstalk in epithelial cell migration. BMC cell biology 17 23441967
2011 Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival. Histopathology 17 22175896
2016 Downregulation of DOCK1 sensitizes bladder cancer cells to cisplatin through preventing epithelial-mesenchymal transition. Drug design, development and therapy 16 27660415
2022 TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation. Biochimica et biophysica acta. Molecular basis of disease 15 36179995
2016 RHOG-DOCK1-RAC1 Signaling Axis Is Perturbed in DHEA-Induced Polycystic Ovary in Rat Model. Reproductive sciences (Thousand Oaks, Calif.) 13 27662902
2022 Combinatorial genetics reveals the Dock1-Rac2 axis as a potential target for the treatment of NPM1;Cohesin mutated AML. Leukemia 11 35778533
2018 Mutations in dock1 disrupt early Schwann cell development. Neural development 11 30089513
2021 A DOCK1 Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells. Cancers 10 34771489
2013 Pro-survival effect of Dock180 overexpression on rat-derived H9C2 cardiomyocytes. Medical science monitor basic research 10 23314417
2010 Stochastic Dynamics of Membrane Protrusion Mediated by the DOCK180/Rac Pathway in Migrating Cells. Cellular and molecular bioengineering 10 20473365
2009 Regulation of focal adhesion and cell migration by ANKRD28-DOCK180 interaction. Cell adhesion & migration 10 19458477
2009 Role of DOCK2 and DOCK180 in fetal thymus colonization. European journal of immunology 10 19728314
2020 Identifying and treating ROBO1-ve /DOCK1+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients. The Prostate 9 32687658
2024 Dragon's blood attenuates LPS-induced intestinal epithelial barrier dysfunction via upregulation of FAK-DOCK180-Rac1-WAVE2-Arp3 and downregulation of TLR4/NF-κB signaling pathways. Journal of natural medicines 8 39014275
2021 Interference with circRNA DOCK1 inhibits hepatocellular carcinoma cell proliferation, invasion and migration by regulating the miR-654-5p/SMAD2 axis. Molecular medicine reports 8 34184075
2016 ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation. Small GTPases 8 27562622
2022 Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway. NPJ science of food 7 35655066
2015 Regulatory role of guanine nucleotide exchange factor (GEF) Dock180 phosphorylation on Tyr/Ser in mediation of gastric mucosal Rac1 activation in response to Helicobacter pylori and ghrelin. Inflammopharmacology 7 25957600
2013 The Rac-specific exchange factors Dock1 and Dock5 are dispensable for the establishment of the glomerular filtration barrier in vivo. Small GTPases 7 24365888

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