Nckβ Interacts with Tyrosine-Phosphorylated Disabled 1 and Redistributes in Reelin-Stimulated Neurons

Pramatarova, Albéna; Ochalski, Pawel G.; Chen, Ke-lian; Gropman, Andrea; Myers, Sage; Min, Kyung‐Tai; Howell, Brian W.

doi:10.1128/mcb.23.20.7210-7221.2003

Cited by 83 publications

(92 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…membrane blebbing) and were not included in our immunofluorescence analyses. While it is possible that GFP-Dab1 can multimerize, and become tyrosine phosphorylated, when over-expressed in retinal cultures, Pramatarova et al 15 reported that Dab1GFP, in contrast to Dab1RFP (red fluorescent protein), is not tyrosine-phosphorylated (and therefore is unlikely to exist of a multimer) in transfected Rat-2 fibroblasts. In support of a physiologically relevant response for GFP-Dab1-transfected retinal cells, mutation of a single amino acid in Dab1-L (Y198F) results in abrogation of morphological (neurite formation) and biochemical (SFK activation) properties associated with Dab1-L.…”

Section: Discussionmentioning

confidence: 99%

“…proteins associated with Dab1 phosphotyrosine-198 include SFKs (Fyn, Src and Yes), phosphoinositol 3′-kinase (PI3K) and phospholipase C-gamma1 (PLCγ1), while those associated with Dab1 phosphotyrosine-220/232 include the Crk and Nck families of adaptor proteins (CrkII, CrkL and Nckβ). 12,15,[29][30][31][32] Recent data indicate that phosphorylation of Y220 and Y232 is required for the release of neurons from radial glial fibers and may be required for the regulation of α3 integrin levels which are critical for the detachment of migrating neurons from the radial glia. 13 It is noteworthy that the dynein/ dynactin-associated protein, Lis1, requires phosphorylation at both Y198 and Y220 in order to interact with Dab1, 14 indicating that some downstream effectors require phosphorylation at both SFK and Abl/Crk/Nck tyrosine phosphorylation/recognition sites.…”

Section: Discussionmentioning

confidence: 99%

“…13 Other reports indicate that Lis1 binding to Dab1 is dependent on phosphorylation at either Y198 or Y220 14 and that Nckβ binding requires either Y220 or Y232 phosphorylation. 15 Combined, these data tyrosine residues may be important in the regulation of downstream effectors of Reelin-Dab1 signaling.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hierarchical Disabled-1 Tyrosine Phosphorylation in Src family Kinase Activation and Neurite Formation

Katyal

Gao

Monckton

et al. 2007

Journal of Molecular Biology

View full text Add to dashboard Cite

There are two developmentally regulated alternatively spliced forms of Disabled-1 (Dab1) in the chick retina: an early form (Dab1-E) expressed in retinal precursor cells and a late form (Dab1-L) expressed in neuronal cells. The main difference between these two isoforms is the absence of two Src family kinase (SFK) recognition sites in Dab1-E. Both forms retain two Abl/Crk/Nck recognition sites implicated in the recruitment of SH2 domain-containing signaling proteins. One of the Dab1-L-specific SFK recognition sites, at tyrosine(Y)-198, has been shown to be phosphorylated in Reelin-stimulated neurons. Here, we use Reelin-expressing primary retinal cultures to investigate the role of the four Dab1 tyrosine phosphorylation sites on overall tyrosine phosphorylation, Dab1 phosphorylation, SFK activation and neurite formation. We show that Y198 is essential but not sufficient for maximal Dab1 phosphorylation, SFK activation and neurite formation, with Y232 and Y220 playing particularly important roles in SFK activation and neuritogenesis, and Y185 having modifying effects secondary to Y232 and Y220. Our data support a role for all four Dab1 tyrosine phosphorylation sites in mediating the spectrum of activities associated with Reelin-Dab1 signaling in neurons.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hierarchical Disabled-1 Tyrosine Phosphorylation in Src family Kinase Activation and Neurite Formation

Katyal

Gao

Monckton

et al. 2007

Journal of Molecular Biology

View full text Add to dashboard Cite

show abstract

“…Downstream signaling by the lipoprotein receptors upon binding of reelin leads to tyrosine phosphorylation of disabled-1, a cytosolic adapter protein, resulting in the activation of signaling pathways through tyrosine kinases of the Src family (34,35). In addition to activation of Src family members, disabled-1 phosphorylation also leads to activation of Akt (36) and redistribution of Nckß from the cell body to distal sites of neuronal processes (37). Although the molecular mechanisms involved in the signaling of reelin are partially known, the role of these events in the correct positioning of neurons during migration is still poorly understood.…”

Section: Active Signaling Molecules: Reelin Tenascin and Netrinmentioning

confidence: 99%

The extracellular matrix provides directional cues for neuronal migration during cerebellar development

Porcionatto

2006

Braz J Med Biol Res

View full text Add to dashboard Cite

Normal central nervous system development relies on accurate intrinsic cellular programs as well as on extrinsic informative cues provided by extracellular molecules. Migration of neuronal progenitors from defined proliferative zones to their final location is a key event during embryonic and postnatal development. Extracellular matrix components play important roles in these processes, and interactions between neurons and extracellular matrix are fundamental for the normal development of the central nervous system. Guidance cues are provided by extracellular factors that orient neuronal migration. During cerebellar development, the extracellular matrix molecules laminin and fibronectin give support to neuronal precursor migration, while other molecules such as reelin, tenascin, and netrin orient their migration. Reelin and tenascin are extracellular matrix components that attract or repel neuronal precursors and axons during development through interaction with membrane receptors, and netrin associates with laminin and heparan sulfate proteoglycans, and binds to the extracellular matrix receptor integrins present on the neuronal surface. Altogether, the dynamic changes in the composition and distribution of extracellular matrix components provide external cues that direct neurons leaving their birthplaces to reach their correct final location. Understanding the molecular mechanisms that orient neurons to reach precisely their final location during development is fundamental to understand how neuronal misplacement leads to neurological diseases and eventually to find ways to treat them.

show abstract

“…Both of these proteins regulate MAP kinases, actin cytoskeleton rearrangement, as well as cell migration, growth and differentiation. There are two highly homologous Nck proteins, Nck␣ and Nck␤, both of which are involved in signaling from activated receptors (61,(63)(64)(65). The Nck SH3 domains can bind p21-activated kinases (PAK), the actin-associated Wiscott-Aldrich syndrome protein (WASP), PAK-related kinases (PRK), and the Nck-interacting kinase (NIK), and can activate the Jnk and p38 MAP kinase cascades (54, 66 -73).…”

Section: Discussionmentioning

confidence: 99%

Tyrosine-phosphorylated SOCS3 Interacts with the Nck and Crk-L Adapter Proteins and Regulates Nck Activation

Sitko

Guevara

Cacalano

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Suppressors of cytokine signaling (SOCS) are negative feedback inhibitors of cytokine and growth factor signal transduction. Although the affect of SOCS proteins on the Jak-STAT pathway has been well characterized, their role in the regulation of other signaling modules is not well understood. In the present study, we demonstrate that SOCS3 physically interacts with the SH2/SH3-containing adapter proteins Nck and Crk-L, which are known to couple activated receptors to multiple downstream signaling pathways and the actin cytoskeleton. Our data show that the SOCS3/Nck and SOCS3/Crk-L interactions depend on tyrosine phosphorylation of SOCS3 Tyr 221 within the conserved SOCS box motif and intact SH2 domains of Nck and Crk-L. Furthermore, SOCS3 Tyr 221 forms a YXXP motif, which is a consensus binding site for the Nck and Crk-L SH2 domains. Expression of SOCS3 in NIH3T3 cells induces constitutive recruitment of a Nck-GFP fusion protein to the plasma membrane and constitutive tyrosine phosphorylation of endogenous Nck. Our findings suggest that SOCS3 regulates multiple cytokine and growth factor-activated signaling pathways by acting as a recruitment factor for adapter proteins.The suppressors of cytokine signaling (SOCS) 1 represent a heterogeneous family of proteins characterized by an N-terminal protein-protein interaction domain followed by a conserved 40 amino acid motif known as the SOCS box (1-4). The N termini of SOCS proteins are divergent and can contain SH2 domains, WD40 repeats, SPRY domains, or ankyrin repeats (3, 4). The most well characterized SOCS subfamily is represented by CIS, SOCS1, SOCS2, and SOCS3, which contain a short (ϳ40 amino acids) N-terminal domain and an internal SH2 domain. These proteins have been shown to inhibit Janus kinase (Jak) signaling through SH2-dependent interactions with phosphotyrosine residues on cytokine receptors or in the catalytic loop of Jak kinases, to block downstream activation of the signal transducers and activators of transcription (STATs) (5-13).The SOCS box is also a protein-protein interaction domain and mediates binding to elongin C, a component of a multisubunit E3 ubiquitin ligase. It has been shown to regulate the stability of SOCS proteins as well as SOCS-associated signaling molecules (4, 14 -15). The current models for the mechanisms of SOCS protein function include direct inhibition of Jak-STAT signaling as well as targeting of signal transduction molecules for degradation through the ubiquitination machinery via its association with elongin C (16 -21). A well studied example of the latter mechanism is inhibition of transformation by the TEL-Jak2 oncogenic fusion protein by SOCS1. SOCS1 binds Tel-Jak2 through its SH2 domain and induces its proteasome-mediated destruction (16 -18). Other signaling proteins that are known to be degraded by SOCS include insulin receptor substrate (IRS)-1 and IRS-2, the guanine nucleotide exchange factor (GEF) Vav, and focal adhesion kinase (FAK) (19 -21).Gene-targeting studies have demonstrated the essential role of SOCS1 ...

show abstract

Nckβ Interacts with Tyrosine-Phosphorylated Disabled 1 and Redistributes in Reelin-Stimulated Neurons

Cited by 83 publications

References 51 publications

Hierarchical Disabled-1 Tyrosine Phosphorylation in Src family Kinase Activation and Neurite Formation

Hierarchical Disabled-1 Tyrosine Phosphorylation in Src family Kinase Activation and Neurite Formation

The extracellular matrix provides directional cues for neuronal migration during cerebellar development

Tyrosine-phosphorylated SOCS3 Interacts with the Nck and Crk-L Adapter Proteins and Regulates Nck Activation

Contact Info

Product

Resources

About