| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.81648451 |
| Dab 1 is rapidly phosphorylated when neurons isolated from embryonic brains are stimulated with Reelin , and several tyrosines have been implicated in this response . 0.81648451^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.59591869 |
| Although Reelin and Dab 1 colocalized well shortly after the addition of Reelin , Dab 1 was no longer associated with internalized Reelin . 0.59591869^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| A signaling pathway involving the extracellular protein Reelin and the intracellular adaptor protein Disabled 1 ( Dab 1 ) controls cell positioning during mammalian brain development . ^^^ In dissociated neurons , apoE reduces the level of Reelin induced tyrosine phosphorylation of Dab 1 . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Genetic evidence suggests that interpretation of the Reelin signal by migrating neurons involves two neuronal cell surface proteins , the very low density lipoprotein receptor ( VLDLR ) and the apoE receptor 2 ( ApoER 2 ) as well as a cytosolic adaptor protein , Disabled 1 ( Dab 1 ) . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Mutation of either reelin ( Reln ) or disabled 1 ( Dab 1 ) results in widespread abnormalities in laminar structures throughout the brain and ataxia in reeler and scrambler mice . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The response of cortical plate cells to reelin requires the tyrosine kinase adaptor disabled 1 ( Dab 1 ) . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The reelin ( reln ) and disabled 1 ( dab 1 ) genes both ensure correct neuronal positioning during brain development . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| It is generally believed that reelin , secreted by specific neuronal types such as Cajal Retzius cells , acts at short distance via the extracellular matrix on target neurons , the response of which requires the Dab 1 gene product . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Thyroid hormone regulates reelin and dab 1 expression during brain development . ^^^ The reelin and dab 1 genes are necessary for appropriate neuronal migration and lamination during brain development . ^^^ Since these processes are controlled by thyroid hormone , we studied the effect of thyroid hormone deprivation and administration on the expression of reelin and dab 1 . ^^^ Significantly , thyroid dependent regulation of reelin and dab 1 was confirmed in vivo and in vitro by hormone treatment of hypothyroid rats and organotypic cultures , respectively . ^^^ Our data suggest that the effects of thyroid hormone on neuronal migration may be in part mediated through the control of reelin and dab 1 expression during brain ontogenesis . . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The medial and dorsal cortical plate and Purkinje cells were reelin negative but expressed disabled 1 ( Dab 1 ) mRNA . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Expression of the genes encoding Reelin and Dab 1 during cortical development in turtle , lizard , chick and mammals correlates with architectonic patterns . ^^^ In all species , Reelin is secreted by marginal zone cells , whereas Dab 1 , which mediates the response to Reelin , is synthesized by cortical plate neurons . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Biochemical and genetic arguments show that the extracellular matrix protein Reelin binds to two lipoprotein receptors ( VLDLR and ApoER 2 ) , which relay the Reelin signal inside target neurons by docking the tyrosine kinase adapter disabled 1 ( Dab 1 ) . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin binds to transmembrane receptors , including VLDLR and ApoER 2 , and stimulates tyrosine phosphorylation of Disabled 1 ( Dab 1 ) , which associates with an NPxY motif present in the cytoplasmic domain of the receptors . ^^^ Disruption of reelin , dab 1 , or both the vldr and apoer 2 genes results in similar cell positioning defects in laminated brain regions including the cerebellum , hippocampus , and cerebral cortex . ^^^ Here , we examine the expression pattern of Dab 1 as a first step toward understanding the function of the Reelin signaling pathway in neural retina . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Mutated Reelin , which lacks the CR 50 epitope region , can not form a homopolymer and fails to induce efficient tyrosine phosphorylation of Disabled 1 ( Dab 1 ) , which should occur to transduce the Reelin signal . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Observations on reelin and Dab 1 deficient mice show that reelin and Dab 1 are both required to develop radial cortical organization and a normal maturation gradient . ^^^ On the other hand , the gradient of corticogenesis is directed from outside to inside in all reptiles studied , as well as in mice that are deficient in reelin , Dab 1 , as well as cyclin dependent kinase 5 ( Cdk 5 ) and p 35 . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Mice that are mutant for Reelin or Dab 1 , or doubly mutant for the VLDL receptor ( VLDLR ) and ApoE receptor 2 ( ApoER 2 ) , show disorders of cerebral cortical lamination . ^^^ Absence of alpha3beta1 leads to a reduction of Dab 1 , a signaling protein acting downstream of Reelin . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Reelin ( RELN ) is a glycoprotein secreted preferentially by cortical gamma aminobutyric acid ergic ( GABAergic ) interneurons ( layers 1 and 2 ) that binds to integrin receptors located on dendritic spines of pyramidal neurons or on GABAergic interneurons of layers 3 through 5 expressing the disabled 1 gene product ( DAB 1 ) , a cytosolic adaptor protein that mediates RELN action . ^^^ METHODS : Reelin , GAD ( 65 ) , GAD ( 67 ) , DAB 1 , and neuron specific enolase messenger RNAs ( mRNAs ) and respective proteins were measured with quantitative reverse transcriptase polymerase chain reaction ( RT PCR ) or Western blot analyses . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| There has identified that Dab 1 is one of the intracellular signaling components that respond to Reelin . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In this review , we will first present a brief overview of the current understanding of : ( a ) the biology of reelin ; ( b ) the putative reelin signaling pathways via integrin receptor stimulation ; ( c ) the cytosolic adapter protein DAB 1 , which appears to be operative in the transduction of reelin ' s pleiotropic actions in embryonic , adolescent , and adult brain ; ( d ) the regulation of GABAergic function , including some aspects of GABAergic system development ; and ( e ) dendritic spine function and its role in the regulation of synaptic plasticity . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Disabled 1 ( Dab 1 ) is an intracellular adapter protein that mediates the effect of Reelin on neuronal migration and cell positioning during mammalian brain development . ^^^ To identify components of the Reelin Dab 1 signaling pathway , we searched for proteins that interact with Dab 1 using a yeast two hybrid strategy . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| A hypomorphic allele of dab 1 reveals regional differences in reelin Dab 1 signaling during brain development . ^^^ The disabled 1 ( Dab 1 ) p 80 protein is essential for reelin signaling during brain development . p 80 has an N terminal domain for association with reelin receptors , followed by reelin dependent tyrosine phosphorylation sites and about 310 C terminal residues of unknown function . ^^^ The haploinsufficiency of the p 45 allele of Dab 1 implies that the C terminus of p 80 affects the strength of reelin Dab 1 signaling , yet there is no apparent change in reelin dependent tyrosine phosphorylation of p 45 relative to p 80 . ^^^ Furthermore , the presence of late born cortical plate neurons in the marginal zone reveals a requirement for reelin Dab 1 signaling in late born cortical plate neurons , and helps distinguish models for the cortical inversion in the reeler mutant mouse . . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Furthermore , ectopic Purkinje cells in cdf / cdf mice express an increased level of Dab 1 protein , as previously observed in mice with mutations in genes in the reelin signaling pathway . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| However , in the reeler background , ectopic Reelin induced tyrosine phosphorylation of Dab 1 in the ventricular zone and rescued some , but not all , of the neuroanatomic and behavioral abnormalities characteristic of reeler . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The addition of heterozygosity of either Dab 1 or Reelin mutation to p 35 / causes the extensive migration defects of cortical neurons in the cerebellum . ^^^ In the double null mice of p 35 and either Dab 1 or Reelin , additional migration defects occur in the Purkinje cells in the cerebellum and in the pyramidal neurons in the hippocampus . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In order to know more about potential functions of CNRs we have mapped their expression during mouse nervous system development and compared their expression with that of reelin and its intracellular effector Dab 1 in several tissues . ^^^ In spinal cord , CNRs and Dab 1 are expressed in motoneurons , while reelin is located in adjacent cells . ^^^ In the retina and olfactory system , we observe CNR and reelin expression but not that of Dab 1 . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Mice deficient in Reelin , Disabled 1 ( Dab 1 ) , or both the very low density lipoprotein receptor ( VLDLR ) and the apolipoprotein E receptor 2 ( ApoER 2 ) exhibit identical neuroanatomic defects in laminar structures throughout the brain . ^^^ Reelin is a secreted glycoprotein that binds to VLDLR and ApoER 2 , inducing tyrosine phosphorylation of Dab 1 , an intracellular adapter protein . ^^^ To explore the possibility that Cdk 5 influences the Reelin pathway , we sought to determine whether Dab 1 is a substrate for Cdk 5 . ^^^ Here we show that Cdk 5 phosphorylates Dab 1 on serine 491 in vitro and in vivo , independently of Reelin signaling . ^^^ We also show that ectopic neurons in Cdk 5 deficient mice exhibit reduced levels of Reelin signaling during later stages of cortical development , although Cdk 5 is not required for Reelin induced tyrosine phosphorylation of Dab 1 . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| These precise patterns of neuronal alignment are regulated by an extracellular matrix protein Reelin , and binding of Reelin to its receptors induces tyrosine phosphorylation of the intracellular adaptor protein disabled 1 ( Dab 1 ) . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| After Reelin binds to its receptors , the Reelin signal is transduced through tyrosine phosphorylation of the intracellular adaptor protein disabled 1 ( Dab 1 ) . ^^^ The reelin gene deficient mouse , reeler , and Dab 1 deficient mouse , yotari , show disrupted positioning of neurons . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin is a large secreted protein that controls cortical layering by signaling through the very low density lipoprotein receptor and apolipoprotein E receptor 2 , thereby inducing tyrosine phosphorylation of the adaptor protein Disabled 1 ( Dab 1 ) and suppressing tau phosphorylation in vivo . ^^^ Reelin signaling components are enriched in axonal growth cones , where tyrosine phosphorylation of Dab 1 is increased in response to Reelin . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Binding of Reelin to ApoER 2 and VLDLR induces phosphorylation of Dab 1 , which binds to the intracellular domains of both receptors . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In contrast , Dab 1 , the intracellular adaptor protein thought to function in Reelin signaling , was expressed in cells having positions consistent with their identification as SPNs and PPNs . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| We illustrate this modification by the cloning of a new gene which is differentially expressed in normal , reelin and Dab 1 mutant mice and is a candidate member of the Reelin signalling pathway involved in brain development . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In mammals , a `` reelin signal ' ' is activated when reelin , secreted by Cajal Retzius neurons , binds to receptors of the lipoprotein receptor family on the surface of cortical plate cells , and triggers Dab 1 phosphorylation . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Dab 1 function depends on its tyrosine phosphorylation , which is stimulated by Reelin , an extracellular signaling molecule . ^^^ Reelin increases the stoichiometry of Dab 1 phosphorylation and downregulates Dab 1 protein levels . ^^^ Reelin binds to various cell surface receptors , including two members of the low density lipoprotein receptor family that also bind to Dab 1 . ^^^ Mutations in Dab 1 , its phosphorylation sites , Reelin , or the Reelin receptors cause a common phenotype . ^^^ However , the molecular mechanism whereby Reelin regulates Dab 1 tyrosine phosphorylation is poorly understood . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| RESULTS : We show that Reelin activates members of the Src family of non receptor tyrosine kinases ( SFKs ) and that this activation is dependent on the Reelin receptors apoER 2 and VLDLR and the adaptor protein Dab 1 . ^^^ Increased Dab 1 protein expression in fyn deficient mice implies a response to impaired Reelin signaling that is also observed in mice lacking Reelin or its receptors . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Disabled 1 ( Dab 1 ) forms part of the Reelin Dab 1 signalling pathway that controls neuronal positioning during brain development ; Dab 1 deficiency gives rise to a reeler like inversion of cortical layers . ^^^ The earliest Dab 1 signal was detected at 7 gestational weeks ( GW ) , the stage of transition from preplate to cortical plate , suggesting a role of the Reelin Dab 1 signalling pathway in preplate partition . ^^^ Furthermore , a subset of Cajal Retzius cells in the marginal zone colocalized Dab 1 and Reelin , and may thus represent a novel target of the Reelin Dab 1 signalling pathway . . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The gene encoding disabled 1 ( DAB 1 ) , the intracellular adaptor of the Reelin pathway , reveals unusual complexity in human and mouse . ^^^ The Disabled 1 ( Dab 1 ) gene encodes a key regulator of Reelin signaling . ^^^ The DAB 1 protein docks to the intracellular part of the Reelin very low density lipoprotein receptor and apoE receptor type 2 and becomes tyrosine phosphorylated following binding of Reelin to cortical neurons . ^^^ In mice , mutations of Dab 1 and Reelin generate identical phenotypes . ^^^ In humans , Reelin mutations are associated with brain malformations and mental retardation ; mutations in DAB 1 have not been identified . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Mice lacking Reelin ( Reln ) , double knockouts lacking the VLDL receptor ( VLDLR ) and ApoE receptor 2 ( ApoER 2 ) , and mice lacking disabled 1 ( Dab 1 ) display increased levels of phosphorylated tau . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Localization of ApoER 2 , VLDLR and Dab 1 in radial glia : groundwork for a new model of reelin action during cortical development . ^^^ Here we provide evidence that the reelin receptor machinery , including the lipoprotein receptors ApoER 2 and VLDLR along with the cytoplasmic adaptor protein Dab 1 , is located in radial glia precursors whose processes span the entire cortical wall from the ventricular zone to the pial surface . ^^^ Moreover , in reeler mice , defective in reelin , decreased levels of Dab 1 in the ventricular zone correspond to an accumulation of the protein in radial end feet beneath the pia matter . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin , Disabled 1 ( Dab 1 ) , apolipoprotein E receptor 2 ( ApoER 2 ) , and very low density lipoprotein receptor ( VLDLR ) participate in a signaling pathway required for layer formation during mammalian brain development . ^^^ Binding of Reelin to ApoER 2 and VLDLR induces a rapid increase in tyrosine phosphorylation of Dab 1 , an adaptor protein that associates with the cytoplasmic domain of the receptors . ^^^ Consistent with the binding data , the level of Reelin induced Dab 1 phosphorylation was more severely reduced in neurons lacking ApoER 2 than in neurons lacking VLDLR . ^^^ Finally , there was a complete absence of Reelin induced tyrosine phosphorylation of Dab 1 in cortical neurons from mice lacking both ApoER 2 and VLDLR . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| We studied the postnatal development of the radial glial scaffold in the dentate gyrus of reeler mice , lacking the extracellular matrix protein Reelin , in scrambler mice , deficient in the intracellular adaptor protein disabled 1 ( Dab 1 ) , which is required for the transmission of the Reelin signal into the cell , and in mutant mice lacking the Reelin receptors apolipoprotein receptor 2 ( ApoER 2 ) and / or the very low density lipoprotein receptor ( VLDLR ) , known to transmit the Reelin signal via Dab 1 . ^^^ By immunolabeling for the glial fibrillary acidic protein ( GFAP ) , we show that a regular dentate radial glial scaffold fails to form in mutants deficient of Reelin , Dab 1 , and VLDLR and ApoER 2 . ^^^ Our results suggest that Reelin signaling via ApoER 2 , VLDLR , and Dab 1 is required for the formation of a regular radial glial scaffold in the dentate gyrus . . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Although it is not required for splitting of the cortical pre plate into the marginal zone and sub plate , a process that is affected in absence of the reelin and / or Dab 1 , it is substantial for the later born neurons to bypass sub plate neurons and to enter into the embryonal cortical plate . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reeler and yotari mice , which are mutant for Reelin or Dab 1 , respectively , show disorders of cerebral cortical lamination . ^^^ The present quantitative study shows that the distribution pattern of layer 5 neurons , but not layer 6 neurons , differs between reeler and yotari mice , suggesting that the Reelin and Dab 1 proteins may play different roles in the migration and cell positioning of layer 5 neurons . . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Formation of the mammalian six layered neocortex depends on a signaling pathway that involves Reelin , the very low density lipoprotein receptor , the apolipoprotein E receptor 2 ( ApoER 2 ) , and the adaptor protein Disabled 1 ( Dab 1 ) . ^^^ Recruitment of the Dab 1 PTB domain to PI rich regions of the plasma membrane may facilitate association with the Reelin receptor cytoplasmic tails to transduce a critical positional cue to migrating neurons . . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Extracellular Reelin binds to receptors of the lipoprotein receptor family and induces tyrosine phosphorylation of the adaptor Dab 1 . ^^^ First , we show that the central part of Reelin is involved in receptor binding and signal activation as reflected in Dab 1 phosphorylation . ^^^ Third , we present preliminary studies by in situ hybridization that demonstrate regulated expression of Reelin receptors and Dab 1 by radial precursors in the ventricular zone . . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Dab 1 is a key cytoplasmic mediator in Reelin signaling that controls cell positioning in the developing central nervous system , whereas Dab 2 is an adapter protein that plays a role in endocytosis . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In developing mammalian ( mouse ) brain , Reelin ( Reln ) is secreted by the Cajal Retzius ( CR ) neurons in the marginal zone , binds apolipoprotein E receptor 2 ( ApoER 2 ) and very low density lipoprotein receptor ( Vldlr ) , and induces the phosphorylation of the downstream cytoplasmic molecule disabled 1 ( Dab 1 ) in cortical plate neurons . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The Reelin signaling pathway controls neuronal positioning during mammalian brain development by binding to the very low density lipoprotein receptor and apolipoprotein E receptor 2 , and signaling through the intracellular adapter protein Disabled 1 ( Dab 1 ) . ^^^ To identify new components in the Reelin signaling pathway , we used a yeast two hybrid screen to select Dab 1 interacting proteins . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Phosphatidylinositol 3 kinase interacts with the adaptor protein Dab 1 in response to Reelin signaling and is required for normal cortical lamination . ^^^ Reelin signaling requires activation of Src family kinases as well as tyrosine phosphorylation of the intracellular adaptor protein Disabled 1 ( Dab 1 ) . ^^^ Here we demonstrate that PI3K activation by Reelin requires Src family kinase activity and depends on the Reelin triggered interaction of Dab 1 with the PI3K regulatory subunit p85alpha . ^^^ Efficient Dab 1 phosphorylation and activation of the Reelin signaling cascade is impaired by cholesterol depletion of the plasma membrane . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| We could further demonstrate that this signaling requires Dab 1 , as the increase in Blbp upon reelin addition failed to occur in Dab 1 / mice . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The Reelin signal is transduced into the cell by the lipoprotein receptors VLDLR and ApoER 2 , leading to tyrosine phosphorylation of the associated intracellular adaptor protein Disabled 1 ( Dab 1 ) . ^^^ Tyrosine phosphorylation of Dab 1 is essential for responding to Reelin , as knock in mice expressing a form of Dab 1 that can not be phosphorylated on tyrosine are indistinguishable from mice lacking Reelin , Reelin receptors or Dab 1 . ^^^ However , Reelin has recently been shown to activate the phosphoinositide 3 kinase ( PI 3 K ) dependent kinase , Akt , as well as Src family kinases in wild type but not Dab 1 / primary embryonic neuronal cultures . ^^^ Using pharmacological inhibitors and mice harboring mutant alleles of Dab 1 , we show here that tyrosine phosphorylation , but not the carboxyl terminal region , of Dab 1 is required for Reelin induced activation of Akt and Src family kinases . ^^^ Additionally , although Fyn is an important regulator of Dab 1 , Fyn deficiency does not prevent acute Reelin induced Akt activation . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Unique features in the present case were ( 1 ) bilateral periventricular undulating cortical ribbon like structures mimicking fused gyri and sulci , associated with aberrant reelin expression , ( 2 ) large dysplastic neocortical neurons positive for phosphorylated neurofilament , calbindin D28K , tuberin , hamartin , doublecortin , LIS 1 , reelin and Dab 1 , ( 3 ) derangement of radial glial fibers , and ( 4 ) disorganized cerebellar cortex and heterotopic gray matter composed exclusively of granule cells in the cerebellar deep white matter . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Dab 1 and Lis 1 bound in a reelin induced phosphorylation dependent manner . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin is secreted by Cajal Retzius cells and binds to the very low density lipoprotein receptor and apolipoprotein E receptor type 2 receptors on the surface of CP cells , inducing tyrosine phosphorylation of the intracellular Dab 1 adapter . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The tyrosine phosphorylation sites of the Disabled 1 ( Dab 1 ) docking protein are essential for the transmission of the Reelin signal , which regulates neuronal placement . ^^^ The SH 2 domain of Nck beta but not Nck alpha binds Dab 1 phosphorylated on the Reelin regulated site , Y 220 , or on Y 232 . ^^^ Nck beta is coexpressed with Dab 1 in the developing brain and in cultured neurons , where Reelin stimulation leads to the redistribution of Nck beta from the cell soma into neuronal processes . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Disabled 1 ( Dab 1 ) is an adapter molecule in a signaling pathway , stimulated by reelin , that controls cell positioning in the developing brain . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Disabled 1 ( Dab 1 ) is an adapter molecule in a signaling pathway , stimulated by Reelin , which controls cell positioning in the developing brain . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Dab 1 function in vivo depends on tyrosine phosphorylation , which is stimulated by extracellular Reelin and requires Src family kinases . ^^^ Reelin signaling also negatively regulates Dab 1 protein levels in vivo , and reduced Dab 1 levels may be part of the mechanism that regulates neuronal migration . ^^^ We have made use of mouse embryo cortical neuron cultures in which Reelin induces Dab 1 tyrosine phosphorylation and Src family kinase activation . ^^^ We have found that Dab 1 is normally stable , but in response to Reelin it becomes polyubiquitinated and degraded via the proteasome pathway . ^^^ The requirements for Reelin induced degradation of Dab 1 in vitro correctly predict Dab 1 protein levels in vivo in different mutant mice . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin promotes hippocampal dendrite development through the VLDLR / ApoER2 Dab 1 pathway . ^^^ Reelin is a secreted glycoprotein that regulates neuronal positioning in cortical brain structures through the VLDLR and ApoER 2 receptors and the adaptor protein Dab 1 . ^^^ Addition of Reelin interfering antibodies , receptor antagonists , and Dab 1 phosphorylation inhibitors prevented dendrite outgrowth from normal neurons , whereas addition of recombinant Reelin rescued the deficit in reeler cultures . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Here we show the following : ( 1 ) the central fragment is necessary and sufficient for receptor binding in vitro and for Dab 1 phosphorylation in neuronal cultures ; ( 2 ) Reelin does not bind the protocadherin cadherin related neuronal receptor ( CNR 1 ) as reported previously ; ( 3 ) Reelin and its central fragment are equally able to rescue the reeler phenotype in a slice culture assay ; and ( 4 ) anti receptor antibodies can induce Dab 1 phosphorylation but do not correct the reeler phenotype in slices . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin binding to apolipoprotein E receptor 2 ( ApoER 2 ) and very low density lipoprotein receptor ( VLDLR ) leads to phosphorylation of disabled 1 ( Dab 1 ) , an adaptor protein which associates with the intracellular domains of both receptors . ^^^ Coreceptors for Reelin have been postulated to be necessary for Dab 1 phosphorylation . ^^^ Induced dimerization of Dab 1 in HEK 293 cells leads to its phosphorylation even in the absence of Reelin receptors . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| After Reelin binds the lipoprotein receptors on migrating neurons , the intracellular adaptor protein Disabled 1 ( Dab 1 ) becomes phosphorylated , ultimately resulting in the proper positioning of cortical neurons . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The Reelin Disabled 1 ( Dab 1 ) signaling pathway plays a critical role in neuronal cell positioning in the brain . ^^^ A key difference between the two forms is the exclusion in chDab 1 E of two Src related tyrosine kinase recognition sites implicated in Reelin mediated Dab 1 tyrosine phosphorylation . ^^^ We propose that alternative splicing of chDab 1 represents an effective and flexible way of regulating the Reelin Dab 1 signaling pathway in a mixed cell population , by ensuring that secreted Reelin activates the signaling cascade only in target neuronal cells . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin action requires tyrosine phosphorylation of the intracellular protein Dab 1 by Src family kinases . ^^^ Of these , the Crk family proteins ( CrkL , CrkI , and CrkII ) , bind significant quantities of Dab 1 when embryonic cortical neurons are exposed to Reelin . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Disabled 1 ( Dab 1 ) functions as a critical adapter protein in the Reelin signaling pathway to direct proper positioning of neurons during brain development . ^^^ Reelin stimulates phosphorylation of Dab 1 on tyrosines 198 and 220 , and phosphorylated Dab 1 is likely to interact with downstream signaling proteins that contain Src homology 2 ( SH 2 ) domains . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Here , we have analysed two major components of the reelin pathway involved in neuronal migration and cortical development , that is , p 35 and disabled 1 ( dab 1 ) , in gangliogliomas . ^^^ |
|
| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The cytoplasmic adaptor protein Disabled 1 ( Dab 1 ) is necessary for the regulation of neuronal positioning in the developing brain by the secreted molecule Reelin . ^^^ Binding of Reelin to the neuronal apolipoprotein E receptors apoER 2 and very low density lipoprotein receptor induces tyrosine phosphorylation of Dab 1 and the subsequent activation or relocalization of downstream targets like phosphatidylinositol 3 ( PI 3 ) kinase and Nckbeta . ^^^ Disruption of Reelin signaling leads to the accumulation of Dab 1 protein in the brains of genetically modified mice , suggesting that Reelin limits its own action in responsive neurons by down regulating the levels of Dab 1 expression . ^^^ Here , we use cultured primary embryonic neurons as a model to demonstrate that Reelin treatment targets Dab 1 for proteolytic degradation by the ubiquitin proteasome pathway . ^^^ The Reelin induced Dab 1 degradation also depends on apoER 2 and very low density lipoprotein receptor in a gene dose dependent manner . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Interaction between Dab 1 and CrkII is promoted by Reelin signaling . ^^^ Reelin induced Dab 1 tyrosine phosphorylation has been implicated in the regulation of neuronal positioning during brain development . ^^^ The CrkII Dab 1 interaction requires tyrosine phosphorylation of Dab 1 at residues 220 or 232 and is promoted by Reelin treatment of embryonic forebrain neurons . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Integrin and the Reelin Dab 1 pathway : a sticky affair . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin , integrin and DAB 1 interactions during embryonic cerebral cortical development . ^^^ Furthermore , Dab 1 , a member of the reelin signaling pathway , can complex with the cytoplasmic region of beta 1 integrin in a reelin dependent manner . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| We also show that reelin is expressed at high levels at the final destination of the migratory process , while the reelin intracellular effector Dab 1 was expressed by cell groups that included the two populations affected . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| To further investigate these studies , brain levels of Reelin protein and mRNA and mRNAs for VLDLR , Dab 1 , and GSK 3 were investigated . ^^^ Quantitative reverse transcriptase polymerase chain reaction analysis of Reelin , VLDL R , Dab 1 , and GSK 3 mRNA species in superior frontal and cerebellar cortices of autistic and control subjects were also performed . ^^^ CONCLUSIONS : Reductions in Reelin protein and mRNA and Dab 1 mRNA and elevations in Reln receptor VLDLR mRNA demonstrate impairments in the Reelin signaling system in autism , accounting for some of the brain structural and cognitive deficits observed in the disorder . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Within this pathway , Disabled 1 ( Dab 1 ) serves as an intracellular adaptor that is tyrosine phosphorylated when Reelin , a secreted glycoprotein , binds to the lipoprotein receptors VLDLR and ApoER 2 on the surface of neurons . ^^^ Furthermore , receptor independent membrane targeting of Dab 1 is required for its interaction with Src and Crk , and disruption of phosphoinositide binding also blocks subsequent Reelin induced tyrosine phosphorylation of Dab1 . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The target cells for reelin express the cytoplasmic adapter protein Dab 1 , which binds to the reelin receptors VLDLR and ApoER 2 . ^^^ In mouse , some Cajal Retzius cells express reelin and VLDLR ; in humans , all the components of the signalling pathway ( Reelin , Dab 1 , VLDLR and ApoER 2 ) are present in subsets of Cajal Retzius cells . ^^^ In sum , the receptor expression patterns are similar in the human and mouse cortical plate but differ in Cajal Retzius and Purkinje cells , which in humans express additional components of the reelin Dab 1 pathway . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Disabled 1 ( Dab 1 ) is an essential adaptor protein that functions in the Reelin signaling pathway and is required for the regulation of neuronal migration during embryonic development . ^^^ Binding of Reelin to these receptors leads to tyrosine phosphorylation of Dab 1 and the initiation of a signaling cascade that results in remodeling of the cytoskeleton . ^^^ Here we have investigated how phosphoinositide binding by the Dab 1 PTB domain influences Reelin signal transduction . ^^^ Our findings in cultured primary neurons that have been transduced with lentiviral constructs expressing mutant Dab 1 forms reveal that phosphoinositide binding by the Dab 1 PTB domain is necessary for proper membrane localization of Dab 1 and for effective transduction of a Reelin signal . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reconstitution of the Reelin signaling pathway in fibroblasts demonstrates that Dab 1 phosphorylation is independent of receptor localization in lipid rafts . ^^^ We have subsequently used these cell lines to study the subcellular localization of ApoER 2 and the VLDL receptor and could demonstrate that receptor mediated Dab 1 phosphorylation does not depend on lipid rafts and that phosphorylated Dab 1 remains bound to the receptor tail when the pathway is activated by Reelin . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Similarly , no rescue of the reeler like phenotype was observed in slices from mutants lacking Disabled 1 ( Dab 1 ) , an adapter protein downstream of Reelin receptors . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Both the phosphoinositide and receptor binding activities of Dab 1 are required for Reelin stimulated Dab 1 tyrosine phosphorylation . ^^^ Reelin stimulated tyrosine phosphorylation of the Dab 1 adaptor protein is required during brain development for Reelin dependent neuron positioning in the cerebral cortex and various other laminated regions . ^^^ Dab 1 contains an amino terminal PTB / PI domain through which it can bind to Reelin receptors and membrane phosphoinositides . ^^^ In neurons , this mutation reduces both basal and Reelin stimulated Dab 1 tyrosine phosphorylation . ^^^ These results support a model in which phospholipids recruit Dab 1 to membranes but do not play a direct role in relaying the Reelin signal , while direct Dab 1 receptor interaction is responsible for relaying the Reelin signal but not for membrane recruitment . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin , a large protein that regulates neuronal migration during embryonic development , activates a conserved signaling pathway that requires its receptors , very low density lipoprotein receptor and apolipoprotein E receptor 2 , the cytoplasmic adaptor protein Disabled 1 ( Dab 1 ) , and Src family kinases ( SFK ) . ^^^ Here , we show that Reelin can regulate NMDA type glutamate receptor activity through a mechanism that requires SFKs and Dab 1 . ^^^ Reelin mediates tyrosine phosphorylation of and potentiates calcium influx through NMDA receptors in primary wild type cortical neurons but not in Dab 1 knock out neurons or in cells in which Reelin binding to its receptors is blocked by a receptor antagonist . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Only a small ( approximately 5 % ) subpopulation of these neurons expresses one of the reelin receptors ( ApoER2 / Lrp8 ) , and all GnRH neurons appear to lack the intracellular adaptor protein Dab 1 , suggesting that the function of reelin is not mediated by the conventional signal transduction pathway . ^^^ Mutants lacking the reelin receptors ApoER 2 and Vldlr , and scrambler mice lacking Dab 1 , showed a normal complement of GnRH neurons in the hypothalamus , confirming that the effect of reelin in their migration is independent of Dab1 . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Spontaneous mouse mutants in GRID 2 and DAB 1 are associated with Lurcher and Reelin , respectively . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In mammalian neurons , overexpression of APP reduced the ability of Reelin to induce Dab 1 tyrosine phosphorylation , suggesting an antagonistic relationship between APP family members and Dab 1 function . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| First , early born and late born interneurons behaved differently in mice lacking Reelin or disabled 1 ( Dab 1 ) . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Reelin and Disabled 1 ( Dab 1 ) are essential for positioning migrating neurons in the developing neocortex . ^^^ Closer examination of the morphology of Dab 1 suppressed neurons at E 20 revealed simplified leading processes that are less likely to contact the marginal zone ( MZ ) , in which high levels of Reelin are expressed . ^^^ These data reveal a cell autonomous role of Dab 1 in dendritogenesis in the neocortex and suggest that remodeling of the leading process of a migrating neuron into a nascent dendrite by Reelin / Dab1 signaling plays an important role in cell positioning . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| After Reelin binds to the receptors , Disabled 1 ( Dab 1 ) , an intracellular adaptor protein that binds to the cytoplasmic tails of the receptors , becomes phosphorylated on tyrosine residues , initiating a signaling cascade that includes activation of Src family kinases and Akt . ^^^ Using primary neuronal cultures stimulated with recombinant Reelin , we find that normal Reelin signaling requires the wild type NFDNPVY sequence and likely the interaction of Apoer 2 with Dab 1 . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Ten years following identification of Reelin as the product of the gene mutated in reeler mice , the signalling pathway activated by Reelin is being progressively unravelled with the identification of lipoprotein receptors as reelin receptors , of the Dab 1 adapter and of some other proximal components in target cells . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Dab 1 is a key effector of the Reelin pathway , which regulates neuronal migration during brain development in vertebrates . ^^^ Because these alternative splicing events give rise to isoforms with different numbers of phosphorylateable tyrosines , we speculate that alternative splicing of the dab 1 gene in zebrafish and in other vertebrates regulates the nature of the cellular response to the Reelin signal . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| We used immunocytochemistry to map the distribution of Reelin and Disabled 1 ( the protein product of the reeler gene , and the intracellular adaptor protein , Dab 1 , involved in its signaling pathway ) in adjacent regions of the developing dorsal horn , from early to late embryonic development . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| The levels of Reelin and Dab 1 tyrosine phosphorylation were reduced , suggesting that the Reelin cascade is affected in Hsf 2 / cortices . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| A protein putatively functioning as an intracellular target for the signal transduction cascade triggered by RELN protein released into the extracellular matrix is termed mouse disabled 1 ( DAB 1 ) and is expressed at comparable levels in the neuroplasm of the PFC and hippocampal pyramidal neurons , cerebellar Purkinje neurons of schizophrenia patients , and nonpsychiatric subjects ; these three types of neurons do not express RELN protein . ^^^ In the same samples of temporal cortex , we found a decrease in RELN protein of approximately 50 % but no changes in DAB 1 protein expression . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Dab 1 , the target adapter protein that presumably mediates transcription regulation via the extrasynaptic actions of Reln , is expressed predominantly in pyramidal neurons , but it can also be detected in a small population of GABAergic neurons that are neither horizontal nor bitufted neurons . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In mice , the Dab 1 protein is thought to function downstream of the extracellular protein Reln during neuronal positioning . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| In vivo , absence of Reln correlates with up regulation of the docking protein Dab 1 and decreased Dab 1 tyrosine phosphorylation . ^^^ Loss of the Reln receptor proteins , apolipoprotein receptor 2 and very low density lipoprotein receptor , results in a Reln like phenotype accompanied by increased Dab 1 protein expression . ^^^ Complete loss of Dab 1 , however , recapitulates the Reln phenotype . ^^^ CONCLUSIONS : Dab 1 is downregulated by the Reln signal in neurons in the absence of tyrosine phosphorylation . ^^^ Dab 1 tyrosine phosphorylation sites and not downregulation of Dab 1 protein are required for Reln signaling . . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Experiments in rodents ( including wild type or reeler heterozygous mice ) and non human primates suggest the Reln secreted in the extracellular matrix of neocortex , via integrin receptors , modulates the function of the adaptor protein DAB 1 ( drosophila disable gene ) homologous product ) thereby participating in dynamic processes associated with plasticity changes in dendrites , dendritic spines and their synapses . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| Increased cell motility was also induced by knockdown of downstream components of the RELN pathway , including ApoER 2 , VLDLR , and DAB 1 . ^^^ Treatment of pancreatic cancer cells with histone deacetylase inhibitors , valproic acid and suberoylanilide hydroxamic acid , restored the expression of RELN and DAB 1 and markedly inhibited their migration . ^^^ |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P78509 and O75553 |
Pubmed |
SVM Score :0.0 |
| NA |
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