Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1

Ignelzi, Michael A.; Miller, Danette R.; Soriano, Philippe; Maness, Patricia F.

doi:10.1016/0896-6273(94)90339-5

Cited by 264 publications

(193 citation statements)

References 52 publications

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“…Some other pathways might thus be responsible for the tyrosine phosphorylation of p130 cas in high density cultures. It has been reported that some cell adhesion molecules such as L1 and N-CAM require Src family kinases for their function (38,39). These molecules might be stimulated in high density cultures and affected downstream signal transduction molecules including Src family kinases.…”

Section: Discussionmentioning

confidence: 99%

Activation of pp60 Depending on Cell Density in PC12h Cells

Kobayashi¹,

Okumura²,

Nakamoto³

et al. 1997

Journal of Biological Chemistry

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The Src family tyrosine kinases and their substrates are involved in cell-cell and cell-matrix interactions. We found that in PC12h cells, an increase of cell density enhanced the tyrosine phosphorylation levels of several intracellular proteins including p130 cas . Because it is a possible substrate for Src family kinases, we measured pp60 c-src activity and found that it was higher in high density cultures than in low density cultures. This phenomenon was also observed in PC12 (the parental cell line of the PC12h subclone), Balb/c 3T3, Swiss 3T3, and Hela cells. One of the possible mechanisms regulating the kinase activity of pp60 c-src is the phosphorylation and dephosphorylation of its negative regulatory site located at its C terminus. However, the tyrosine phosphorylation level of the regulatory site did not change depending on cell density. Subcellular fractionation showed that in high density culture, pp60 c-src was translocated from detergent-soluble to detergent-insoluble fractions. These results suggest that cell-cell interaction might induce the activation of pp60 c-src without changing its tyrosine phosphorylation levels.

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Section: Discussionmentioning

confidence: 99%

Activation of pp60 Depending on Cell Density in PC12h Cells

Kobayashi¹,

Okumura²,

Nakamoto³

et al. 1997

Journal of Biological Chemistry

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“…Although the function of Src must be at least partially redundant with that of other proteins (for example, Src-deficient mice do not exhibit major defects in synaptic function; see refs. 3 and 43 for review), impaired neurite outgrowth was observed when cerebellar neurons derived from Src-deficient mice were cultured on a substrate of the L1 cell adhesion molecule (44).…”

Section: Discussionmentioning

confidence: 99%

Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity

Onofri

Giovedì

Vaccaro

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Synapsin I is a synaptic vesicle-associated phosphoprotein that has been implicated in the formation of presynaptic specializations and in the regulation of neurotransmitter release. The nonreceptor tyrosine kinase c-Src is enriched on synaptic vesicles, where it accounts for most of the vesicle-associated tyrosine kinase activity. Using overlay, affinity chromatography, and coprecipitation assays, we have now shown that synapsin I is the major binding protein for the Src homology 3 (SH3) domain of c-Src in highly purified synaptic vesicle preparations. The interaction was mediated by the proline-rich domain D of synapsin I and was not significantly affected by stoichiometric phosphorylation of synapsin I at any of the known regulatory sites. The interaction of purified c-Src and synapsin I resulted in a severalfold stimulation of tyrosine kinase activity and was antagonized by the purified c-Src-SH3 domain. Depletion of synapsin I from purified synaptic vesicles resulted in a decrease of endogenous tyrosine kinase activity. Portions of the total cellular pools of synapsin I and Src were coprecipitated from detergent extracts of rat brain synaptosomal fractions using antibodies to either protein species. The interaction between synapsin I and c-Src, as well as the synapsin I-induced stimulation of tyrosine kinase activity, may be physiologically important in signal transduction and in the modulation of the function of axon terminals, both during synaptogenesis and at mature synapses.Synapsin I is the major synaptic vesicle protein that binds to the Src homology 3 (SH3) domains of the adapter protein Grb2 in vitro (1). This interaction is mediated by domain D of synapsin I, a 23-kDa proline-rich, strongly basic domain located in the COOH-terminal portion of synapsin I (2). It seemed possible that domain D or other proline-rich regions in synapsin I might interact with other SH3 domain-containing proteins within the nerve terminal and that these interactions might have a physiological role in presynaptic function. One such candidate, the SH3 domain-containing nonreceptor tyrosine kinase c-Src, is expressed at high levels in postmitotic neurons and is enriched on synaptic vesicles, where it accounts for most of the vesicle-associated tyrosine kinase activity (3-6). Using purified components in vitro, we now report that a domain Dmediated interaction of synapsin I with the SH3 domain of c-Src results in a 5-fold activation of the catalytic activity of c-Src. We also present studies employing a variety of biochemical techniques that serve to further characterize the specificity, subcellular location, regulation, and potential functional consequences of the c-Src͞synapsin I interaction.

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“…The other class, a non receptor-type kinases, includes the family of Src proto-oncogene-related kinases. Several members of this family including c-Src, Fyn, Yrk c-Yes and Lck have been described in developing and regenerating neurons (Grant et al, 1992;Ignelzi et al, 1994;Yagi 1994;Omri et al, 1996;Van Tan et al, 1996) but their functions in these cells have not been clearly elucitated. p60 src has been fully characterized in the neural retina (Sorge et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Retinal dysplasia in mice lacking p56lck

et al. 1998

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The product of the proto-oncogene p56 lck is a nonreceptor tyrosine kinase member of the Src family. It is found in T cells (Marth et al., 1985(Marth et al., , 1988 and in the mouse brain (Omri et al., 1996;Van Tan et al., 1996). In this report, we describe experiments showing that Lck is present in the mouse retina neurons. Lck gene expression was identi®ed after isolating and sequencing the speci®c 5' and 3' part of the cDNA obtained by RT ± PCR. In adult retina Lck immunoreactivity was most abundant in photoreceptor cells and within the outer plexiform layers. Staining was also observed in the inner nuclear and plexiform layers. In transgenic mice, the disruption of the Lck gene had serious consequences on the organization of the retina causing retinal dysplasia. These mice have partial retinal detachment with infolding and rosette formation in the photoreceptor sheet. These retinal abnormalities observed in Lck de®cient mice lead to the loss of normal architecture of the photoreceptor and the inner nuclear layers, and provide an important role of Lck protein in the retina development. The lack of the Lck protein produces a spectrum of retinal pathology that resembles human retinopathy of prematurity (ROP).

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Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1

Cited by 264 publications

References 52 publications

Activation of pp60 Depending on Cell Density in PC12h Cells

Activation of pp60 Depending on Cell Density in PC12h Cells

Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity

Retinal dysplasia in mice lacking p56lck

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