| 1995 |
p130Cas (BCAR1) interacts directly with FAK via its SH3 domain binding to the proline-rich region of FAK (APPKPSR, residues 711-717), as demonstrated by yeast two-hybrid screen and confirmed by co-immunoprecipitation in mouse fibroblasts. |
Yeast two-hybrid screen, co-immunoprecipitation |
Proceedings of the National Academy of Sciences of the United States of America |
High |
7479864
|
| 1995 |
p130Cas becomes tyrosine-phosphorylated during integrin-mediated cell adhesion to extracellular matrix substrata, dependent on integrin ligation and actin cytoskeleton integrity (blocked by cytochalasin D), but independent of cell adhesion in v-src-transformed cells. |
Western blot, immunoprecipitation, cytochalasin D inhibition |
The Journal of biological chemistry |
High |
7545676
|
| 1996 |
The C-terminal region of p130Cas directly binds both SH2 and SH3 domains of Src kinase; the SH3-binding site maps to RPLPSPP near the C-terminus, and both this site and Tyr762 are required for Src association, while the substrate domain mediates binding to v-Crk via its SH2 domain. |
GST fusion protein pulldown, mutagenesis |
The Journal of biological chemistry |
High |
8621540
|
| 1996 |
Individual domains of p130Cas associate with distinct binding partners: FAK, v-Src, and v-Crk binding sites are mapped to distinct regions of p130Cas, and many interactions are dependent on the tyrosine-phosphorylation state of p130Cas. |
In vitro domain-binding assays, domain mapping |
Oncogene |
Medium |
8649789
|
| 1997 |
FAK phosphorylates p130Cas in vitro and in cells upon fibronectin stimulation (via a FAK/Src 1-298 complex), and FAK-induced phosphorylation of p130Cas promotes SH2-domain-dependent binding of the Nck adaptor protein to p130Cas. |
In vitro kinase assay, co-immunoprecipitation, fibronectin stimulation |
Molecular and cellular biology |
High |
9032297
|
| 1997 |
During bacterial uptake, p130Cas and FAK are phosphorylated and recruited to peripheral focal complexes in HeLa cells; Yersinia YopH (active PTPase) dephosphorylates p130Cas and FAK and disrupts these complexes, blocking uptake. Inactive YopH co-localizes with and binds the tyrosine-phosphorylated forms of FAK and p130Cas. |
Co-localization, immunoprecipitation, PTPase activity assays |
The EMBO journal |
High |
9171345
|
| 1997 |
RAFTK (Pyk2) directly phosphorylates the substrate domain of p130Cas in vitro; full phosphorylation of p130Cas requires cooperation between RAFTK and Src kinases, with the C-terminal domain of p130Cas requiring RAFTK autophosphorylation site Tyr402 (which mediates Src binding). |
In vitro kinase assay with purified domains, mutagenesis of Tyr402 |
The Journal of biological chemistry |
High |
9242628
|
| 1998 |
p130Cas (BCAR1) is a mediator of FAK-promoted cell migration; FAK mutant P712/715A (which reduces p130Cas association) fails to promote migration, while co-expression of p130Cas enhances migration and the p130Cas SH3 domain alone acts as a dominant negative inhibitor of migration. |
FAK mutant expression, migration assay, co-immunoprecipitation |
The Journal of cell biology |
High |
9425168
|
| 1998 |
Mice lacking p130Cas (Crkas/BCAR1) die in utero with cardiovascular defects, disorganized myofibrils, and impaired actin stress fiber formation in fibroblasts; activated Src in Cas-deficient fibroblasts fails to induce full transformation due to insufficient actin accumulation in podosomes. |
Knockout mouse generation, histology, electron microscopy, primary fibroblast analysis |
Nature genetics |
High |
9697697
|
| 1998 |
Angiotensin II induces tyrosine phosphorylation of p130Cas in vascular smooth muscle cells via a pathway requiring c-Src family kinase activity, intracellular Ca2+, and protein kinase C; phosphorylated p130Cas then associates with protein kinase C-alpha and pp120, with c-Src constitutively associated. |
Immunoprecipitation, kinase inhibitors, chelators, Western blot |
Circulation research |
Medium |
9648724
|
| 1998 |
Growth hormone stimulates formation of a multiprotein signaling complex centered on p130Cas and CrkII, including c-Src, c-Fyn, tensin, paxillin, IRS-1, p85/PI3K, C3G, SHC, Grb-2, Sos-1, c-Cbl, and Nck; this complex formation correlates with JNK/SAPK activation. |
Co-immunoprecipitation, kinase activity assays |
The Journal of biological chemistry |
Medium |
9837978
|
| 1999 |
PTEN dephosphorylates FAK and decreases tyrosine phosphorylation of both FAK and p130Cas; p130Cas overexpression reverses PTEN inhibition of cell invasion and migration without affecting PTEN-dependent growth suppression, and p130Cas cannot be directly dephosphorylated by PTEN in vitro or shown to interact with PTEN in cells. |
Overexpression, in vitro phosphatase assay, co-immunoprecipitation, invasion assays |
Cancer research |
High |
9927060
|
| 1999 |
p130Cas-deficient fibroblasts exhibit significant defects in cell movement, migration toward fibronectin, and cell spreading; re-expression of p130Cas rescues these defects, establishing a direct role for p130Cas in promoting cell motility. |
Knockout fibroblast re-expression rescue, wound healing assay, transwell migration assay, cell spreading assay |
Biochemical and biophysical research communications |
High |
10448062
|
| 1999 |
MCSP (melanoma chondroitin sulphate proteoglycan) stimulation recruits tyrosine-phosphorylated p130Cas and activates Cdc42; MCSP-induced cell spreading is dependent on active Cdc42, the Cdc42-associated kinase Ack-1, and tyrosine phosphorylation of p130Cas; Ack-1 and Cdc42 inhibition abrogates MCSP-induced p130Cas phosphorylation. |
Co-immunoprecipitation, dominant negative constructs, cell spreading assay |
Nature cell biology |
Medium |
10587647
|
| 1999 |
The transmembrane PTPase LAR dephosphorylates p130Cas in vitro and in vivo, reducing its protein stability and eliminating it from focal adhesions, leading to apoptosis; restoring p130Cas levels alleviates LAR-induced apoptosis, identifying p130Cas as an in vivo substrate of LAR. |
In vitro phosphatase assay, substrate-trapping mutants, rescue by p130Cas overexpression, immunofluorescence |
Genes to cells : devoted to molecular & cellular mechanisms |
High |
10320483
|
| 2000 |
p130Cas associates with the p85 subunit of PI 3-kinase through its RPLPSPP proline-rich domain (SH3 domain of p85 binding), and this interaction is required for adenovirus internalization mediated by alpha-v integrins; inhibition of p130Cas phosphorylation or deletion of its substrate domain blocks adenovirus cell entry. |
Co-immunoprecipitation, dominant negative constructs, adenovirus internalization assay |
The Journal of biological chemistry |
High |
10799562
|
| 2000 |
p130Cas regulates AND-34 (BCAR3) GEF activity: overexpression of p130Cas (but not an AND-34-binding mutant) inhibits AND-34's Ral GEF activity on RalA, Rap1A, and R-Ras; efficient p130Cas-AND-34 binding requires both the Src-binding domain and a flanking C-terminal region of p130Cas. |
GEF activity assay in cells, co-immunoprecipitation, mutant binding analysis |
The Journal of biological chemistry |
Medium |
10896938
|
| 2000 |
BCAR1 (p130Cas) overexpression confers antiestrogen resistance on ZR-75-1 breast cancer cells, identified as the gene responsible for the BCAR1 locus; the gene encodes a 870 amino acid protein homologous to rat p130Cas, located at chromosome 16q23.1. |
Retroviral mutagenesis, cell fusion, cDNA transfection, functional growth assay |
Journal of the National Cancer Institute |
High |
10639512
|
| 2000 |
Caspase-3 cleaves p130Cas at two consensus sites DVPD(416)G and DSPD(748)G during etoposide-induced apoptosis; cleavage correlates with loss of FAK from focal adhesions and attenuation of Cas-paxillin interactions, contributing to focal adhesion complex disassembly. |
In vitro caspase cleavage assay, site-directed mutagenesis, immunofluorescence |
Molecular biology of the cell |
High |
10712510
|
| 2001 |
Integrin-mediated adhesion induces assembly of a macromolecular complex at the cell membrane containing p130Cas, c-Src, and the EGF receptor; both c-Src and p130Cas are required for integrin-dependent phosphorylation of EGF receptor at specific tyrosines (Y845, Y1068, Y1086, Y1173). |
Co-immunoprecipitation, dominant negative constructs, phospho-specific antibodies |
The Journal of biological chemistry |
Medium |
11756413
|
| 2001 |
SHIP2 associates with p130Cas primarily through the SHIP2 SH2 domain; an SH2 domain mutant (R47G) abolishes this interaction and increased SHIP2 expression promotes adhesion, while a catalytic domain deletion mutant inhibits cell spreading. |
Co-immunoprecipitation, SH2 domain mutant, cell adhesion and spreading assays |
Molecular and cellular biology |
Medium |
11158326
|
| 2001 |
FAK and p130Cas localize to sarcomeric Z-lines in cardiac myocytes; expression of the p130Cas-binding proline-rich region 1 of FAK disrupts Cas-FAK association and impairs sarcomere structural stability; Cas alone or with Src modulates atrial natriuretic peptide (ANP) gene promoter activity as a marker of cardiac hypertrophy. |
Immunofluorescence localization, dominant negative expression, luciferase reporter assay |
Molecular biology of the cell |
Medium |
11514617
|
| 2001 |
SAP-1 phosphatase dephosphorylates p130Cas in intact cells and preferentially in vitro; a substrate-trapping SAP-1 mutant induces hyperphosphorylation of p130Cas (dominant negative effect); SAP-1 overexpression inhibits cell spreading on fibronectin and colony formation. |
Substrate-trapping mutagenesis, in vitro phosphatase assay, immunoprecipitation, spreading assay |
The Journal of biological chemistry |
High |
11278335
|
| 2001 |
p130Cas localizes to focal adhesions in podocytes and colocalizes with F-actin at stress fiber ends, distinct from CD2AP which colocalizes with dynamic F-actin at lamellipodia. |
Immunofluorescence, immunoelectron microscopy |
American journal of physiology. Renal physiology |
Medium |
11553524
|
| 2002 |
EphrinA1-induced cytoskeletal reorganization and cell spreading in NIH3T3 cells requires both FAK and p130Cas; MEFs from FAK-/- and p130Cas-/- mice have severe defects in ephrinA1-induced spreading, reversed by re-expression of FAK or p130Cas respectively; EphA2, FAK, and p130Cas are the major ephrin-dependent phosphotyrosyl proteins. |
Knockout MEFs, re-expression rescue, phosphotyrosine analysis, cell spreading assay |
Nature cell biology |
High |
12134157
|
| 2003 |
The p130CAS-CrkII complex functions as a molecular switch in cell motility; KAI1/CD82 expression decreases p130CAS protein levels, reduces p130CAS-CrkII complex formation, and inhibits migration; overexpression of p130CAS in KAI1/CD82-expressing cells restores complex formation and largely reverses migration inhibition. |
Co-immunoprecipitation, overexpression rescue, migration assay |
The Journal of biological chemistry |
Medium |
12738793
|
| 2003 |
Bmx/Etk kinase interacts with p130Cas at membrane ruffles, phosphorylates p130Cas, and promotes Cas-Crk complex formation; a Bmx mutant failing to interact with Cas also fails to induce cell migration; dominant-negative Cas (unable to bind Crk) inhibits Bmx-induced membrane ruffling and migration. |
Co-immunoprecipitation, dominant negative constructs, membrane ruffling and migration assays |
The Journal of biological chemistry |
Medium |
12832404
|
| 2003 |
p140Cap (Cas-associated protein) directly interacts with p130Cas through the p140Cap carboxy-terminal region; the two proteins co-immunoprecipitate and colocalize in lamellipodia; p140Cap overexpression delays cell spreading on fibronectin. |
Affinity chromatography, mass spectrometry, co-immunoprecipitation, immunofluorescence, cell spreading assay |
Molecular biology of the cell |
Medium |
14657239
|
| 2004 |
p130Cas rapidly associates with estrogen receptor alpha (ERα) in a multi-molecular complex containing c-Src and p85/PI3K within 3 minutes of estrogen treatment; this association is c-Src-dependent; p130Cas overexpression enhances estrogen-dependent Src kinase and ERK1/2 activities, while siRNA silencing of p130Cas inhibits estrogen-dependent ERK1/2 activity and cyclin D1 induction. |
Co-immunoprecipitation, siRNA knockdown, kinase activity assays, reporter assays |
Journal of cell science |
High |
15020686
|
| 2005 |
Ajuba (LIM protein) associates with the focal adhesion-targeting domain of p130Cas and acts upstream of p130Cas to localize it to nascent adhesive sites; Ajuba-null cells have reduced p130Cas, Crk, Dock180, and FAK at nascent focal complexes and blunted Rac activation in response to migratory cues. |
Co-immunoprecipitation, knockout mouse fibroblasts, FRET analysis of Rac activation, rescue experiments |
The Journal of cell biology |
High |
15728191
|
| 2005 |
p130Cas overexpression in mammary gland (MMTV-p130Cas mice) leads to mammary epithelial hyperplasia associated with activation of Src, ERK1/2, and Akt; crossing with MMTV-HER2-Neu mice accelerates multifocal mammary tumor development with increased Src and Akt activation; p130Cas siRNA increases apoptosis in HER2-Neu-expressing cells. |
Transgenic mouse models, signaling pathway analysis, siRNA knockdown, tumor latency measurement |
Cancer research |
High |
16651418
|
| 2005 |
NPM-ALK (anaplastic lymphoma kinase fusion) binds p130Cas and induces its phosphorylation in a manner dependent on ALK kinase activity and the adaptor Grb2; p130Cas-/- fibroblasts expressing NPM-ALK show impaired actin depolymerization and are no longer transformed, establishing p130Cas as essential for ALK-mediated transformation. |
Mass spectrometry identification, co-immunoprecipitation, kinase-dead mutant, Grb2 dominant negative, Cas-/- fibroblast reconstitution |
Blood |
High |
16105984
|
| 2006 |
Fibronectin matrix rigidity response requires Fyn (but not endogenous c-Src) recruitment to early adhesions; p130Cas is also required for the rigidity response and is phosphorylated at the leading edge in a Fyn-dependent manner, suggesting force-dependent Fyn phosphorylation of p130Cas. |
Live cell imaging, dominant negative mutants, phosphorylation site analysis, leading edge localization |
Molecular biology of the cell |
Medium |
16597701
|
| 2006 |
Ack1 mediates Cdc42-dependent cell migration through p130Cas: Ack1 forms a signaling complex with Cdc42, p130Cas, and Crk via SH3 domain interactions; Ack1 phosphorylates the substrate domain of p130Cas; siRNA knockdown of either p130Cas or Ack1 blocks Cdc42-induced migration. |
Co-immunoprecipitation, siRNA knockdown, migration assay, phosphorylation analysis |
The Journal of biological chemistry |
High |
17038317
|
| 2007 |
p130CAS is required for netrin-1 signaling: netrin-1 induces p130CAS tyrosine phosphorylation downstream of Src family kinases and upstream of Rac1/Cdc42; inhibiting p130CAS signaling blocks netrin-1-promoted neurite outgrowth and axon attraction; p130CAS RNAi causes defects in commissural axon projection in vivo. |
Biochemical epistasis, RNAi knockdown, in vivo commissural axon projection analysis |
The Journal of neuroscience : the official journal of the Society for Neuroscience |
High |
17251438
|
| 2008 |
Tyrosine phosphorylation of p130Cas is sufficient to activate Rac1 and induce membrane ruffling/lamellipodium formation in SYF cells; the kinase activity of Src (not FAK) is essential for phosphorylating p130Cas within the Src-FAK-p130Cas trimolecular complex at focal adhesions. |
Functional Interaction Trap (FIT) method for selective substrate phosphorylation, Rac1 activation assay, dominant negative FAK |
BMC cell biology |
High |
18793427
|
| 2008 |
Once tyrosine-phosphorylated via integrin signaling, p130Cas binds to Smad3 and reduces Smad3 phosphorylation, inhibiting TGF-β-mediated growth arrest; loss of p130Cas abrogates integrin-mediated suppression of TGF-β/Smad3 signaling. |
Co-immunoprecipitation, loss/gain of function, Smad3 phosphorylation assay, cell cycle analysis |
Molecular biology of the cell |
High |
18321991
|
| 2009 |
Estrogen-dependent formation of ERα-BCAR1 complexes (within ~5 min) is increased by RANKL co-treatment; BCAR1 associates with the RANKL signaling intermediate Traf6 in this complex; BCAR1 siRNA knockdown abolishes estradiol inhibition of osteoclast differentiation, demonstrating BCAR1 is required for estrogen's non-genomic inhibition of NF-κB-mediated osteoclastogenesis. |
Co-immunoprecipitation, siRNA knockdown, osteoclast differentiation assay, NF-κB localization |
Experimental cell research |
Medium |
19331827
|
| 2010 |
Both the N-terminal SH3 domain and the C-terminal Cas-family homology (CCH) domain of p130Cas are required for its localization to focal adhesions (FA targeting requires FAK for the SH3 domain function); deletion of either domain impairs FA localization and tyrosine phosphorylation; both domains are necessary for p130Cas to promote cell migration. |
Live cell microscopy, FRAP, deletion mutants, FA targeting analysis |
The Journal of biological chemistry |
High |
20430882
|
| 2010 |
p130Cas substrate domain (SD) phosphorylation is the sole p130Cas signaling function for promoting leading-edge actin flux and FA assembly/disassembly rates, while the Src-binding domain (SBD) has a distinct function in sustained FA disassembly and cell migration that is independent of its known role in promoting SD phosphorylation. |
Cas-/- MEF rescue with domain mutants, quantitative live cell imaging of FA dynamics and actin flux |
PloS one |
High |
20976150
|
| 2010 |
p130Cas is an essential transducer in ErbB2 transformation: p130Cas forms a functional complex with ErbB2, c-Src, and FAK in transformed cells; p130Cas silencing impairs foci formation, anchorage-independent growth, and in vivo tumor growth; p130Cas overexpression with ErbB2 activates Rac1 and MMP9 secretion, conferring invasive properties. |
siRNA knockdown, in vivo tumor growth, co-immunoprecipitation, Rac1 activation assay, invasion assay |
FASEB journal |
High |
20505116
|
| 2011 |
BCAR1/p130Cas and NEDD9 signal through SRC to promote E-cadherin removal from the cell membrane and lysosomal degradation, negatively regulating E-cadherin expression in human mammary cells without affecting E-cadherin transcription. |
siRNA knockdown, inhibitor studies, pulse-chase/degradation assay, in vivo mammary tumor analysis |
PloS one |
Medium |
21765937
|
| 2011 |
NRP1 (neuropilin-1) co-immunoprecipitates with PDGFRα and selectively mediates PDGF-induced tyrosine phosphorylation of p130Cas; NRP1 siRNA and NRP1 mutants lacking the intracellular domain inhibit PDGF-induced p130Cas phosphorylation and VSMC migration; p130Cas knockdown also inhibits HCASMC migration. |
Co-immunoprecipitation, siRNA knockdown, adenoviral overexpression of NRP1 mutants, migration assays |
The Biochemical journal |
Medium |
21306301
|
| 2012 |
PTPN14 directly dephosphorylates p130Cas specifically at tyrosine residue Y128; homozygous Y128F knock-in CRC cells show reduced migration, colony formation, and slower xenograft tumor growth with decreased AKT phosphorylation; SRC phosphorylates p130Cas Y128. |
Phospho-proteomic screen, knock-in mutagenesis, in vitro phosphatase/kinase assay, xenograft tumor growth |
Oncogene |
High |
22710723
|
| 2012 |
p130Cas-dependent actin remodeling regulates myogenic differentiation: p130Cas phosphorylation (mediated by integrin β3) promotes F-actin formation, nuclear localization of MAL/SRF co-activator, and myotube formation; phosphorylation-defective p130Cas mutant fails to rescue these processes; p130Cas phosphorylation prevents cofilin activation. |
siRNA knockdown, phosphorylation-defective mutant re-expression, F-actin staining, nuclear MAL localization assay |
The Biochemical journal |
High |
22587391
|
| 2013 |
In osteoclasts, p130Cas is required for actin ring formation and bone resorption; p130Cas conditional knockout osteoclasts show reduced Rac1 activity, disrupted Rac1 distribution, and failure of Dock5 (a Rac GEF) to associate with Src or Pyk2, while initial β3-integrin and Src phosphorylation events are intact. |
Osteoclast-specific conditional knockout, actin ring assay, pit formation assay, co-immunoprecipitation of Dock5 |
Journal of bone and mineral research |
High |
23526406
|
| 2014 |
BCAR1 and BCAR3 bind tightly through their C-terminal domains; structure-based interaction-disrupting mutants show that BCAR3-induced antiestrogen resistance critically depends on binding to BCAR1; BCAR3-BCAR1 interaction increases phosphorylated BCAR1 levels and ERK1/2 activity, which mediates resistance. |
Structure-based mutagenesis of interaction interface, co-immunoprecipitation, antiestrogen resistance functional assay, ERK inhibition |
The Journal of biological chemistry |
High |
24584939
|
| 2019 |
p130Cas (BCAR1) is recruited to filopodia tips via its C-terminal Cas family homology domain (CCHD) and acts as a mechanosensitive regulator of filopodia stability, as demonstrated by structured-illumination microscopy mapping and live imaging. |
SIM-based protein localization screen, live imaging, domain deletion analysis (CCHD) |
Current biology : CB |
High |
30639111
|
| 2019 |
p130Cas (Cas) translocates to the nucleus in osteocytes in response to fluid shear stress and alleviates NF-κB activity; osteocyte-specific Cas deficiency increases NF-κB-mediated RANKL expression and osteoclastic bone resorption, leading to osteopenia; shear stress-dependent nuclear Cas translocation was directly observed. |
Osteocyte-specific conditional knockout, nuclear fractionation, live-cell imaging of Cas translocation, NF-κB reporter assays |
Science advances |
High |
31579816
|
| 2021 |
SRC-inhibitor-mediated suppression of p130Cas phosphorylation impairs MYC transcription through a DOCK1-RAC1-β-catenin-dependent mechanism; BCAR1 siRNA sensitizes pancreatic cancer cells to ERK inhibition, identifying BCAR1 as a synthetic lethal interactor with mutant KRAS. |
siRNA/CRISPR genome-scale screen, pathway inhibitors, MYC reporter, DOCK1/RAC1/β-catenin epistasis |
Cell reports |
High |
34192548
|
| 2006 |
Salmonella typhimurium invasion of host cells requires p130Cas; Cas-/- cells are impaired in bacterial internalization, and reconstitution requires the central Cas YXXP repeat domain; FAK overexpression suppresses the invasion defect in Cas-/- cells, suggesting a functional FAK-Cas link in Salmonella invasion. |
Knockout MEFs, reconstitution with domain mutants, genetic suppressor analysis |
Molecular biology of the cell |
High |
16914515
|
| 2011 |
Cyclic stretch induces cell reorientation in a Src family kinase- and p130Cas-dependent manner; knockout or knockdown of p130Cas reduces reorientation upon cyclic stretch, and mutation of stretch-sensitive tyrosines of p130Cas produces identical impairment. |
SYF knockout MEFs, siRNA knockdown, p130Cas tyrosine mutants, cyclic stretch device |
European journal of cell biology |
High |
22178114
|
| 2004 |
p130Cas cleavage occurs during anoikis; overexpression of the p130Cas cleavage product induces apoptosis; caspases and calpain are both involved in cleavage, though additional unidentified proteases may also cleave p130Cas at the early stage of anoikis. |
Cell detachment-induced anoikis assay, cleavage fragment overexpression, caspase/calpain inhibitors |
Journal of cellular biochemistry |
Medium |
14743392
|