Key points are not available for this paper at this time.
Neurotrophins signal through Trk tyrosine kinase receptors and the low-affinity neurotrophin receptor p75NTR. We have shown previously that activation of Trk A tyrosine kinase activity can inhibit p75NTR-dependent sphingomyelin hydrolysis, that caveolae are a localized site for p75NTR signaling, and that caveolin can directly interact with p75NTR. The ability of caveolin to also interact with tyrosine kinase receptors and inhibit their activity led us to hypothesize that caveolin expression may modulate interactions between neurotrophin signaling pathways. PC12 cells were transfected with caveolin that was expressed efficiently and targeted to the appropriate membrane domains. Upon exposure to nerve growth factor (NGF), caveolin-PC12 cells were unable to develop extensive neuritic processes. Caveolin expression in PC12 cells was found to diminish the magnitude and duration of Trk A activationin vivo. This inhibition may be due to a direct interaction of caveolin with Trk A, because Trk A co-immunoprecipitated with caveolin from Cav-Trk A-PC12 cells, and a glutathioneS-transferase-caveolin fusion protein bound to Trk A and inhibited NGF-induced autophosphorylation in vitro. Furthermore, the in vivo kinetics of the inhibition of Trk A tyrosine kinase activity by caveolin expression correlated with an increased ability of NGF to induce sphingomyelin hydrolysis through p75NTR. In summary, our results suggest that the interaction of caveolin with neurotrophin receptors may have functional consequences in regulating signaling through p75NTR and Trk A in neuronal and glial cell populations. Neurotrophins signal through Trk tyrosine kinase receptors and the low-affinity neurotrophin receptor p75NTR. We have shown previously that activation of Trk A tyrosine kinase activity can inhibit p75NTR-dependent sphingomyelin hydrolysis, that caveolae are a localized site for p75NTR signaling, and that caveolin can directly interact with p75NTR. The ability of caveolin to also interact with tyrosine kinase receptors and inhibit their activity led us to hypothesize that caveolin expression may modulate interactions between neurotrophin signaling pathways. PC12 cells were transfected with caveolin that was expressed efficiently and targeted to the appropriate membrane domains. Upon exposure to nerve growth factor (NGF), caveolin-PC12 cells were unable to develop extensive neuritic processes. Caveolin expression in PC12 cells was found to diminish the magnitude and duration of Trk A activationin vivo. This inhibition may be due to a direct interaction of caveolin with Trk A, because Trk A co-immunoprecipitated with caveolin from Cav-Trk A-PC12 cells, and a glutathioneS-transferase-caveolin fusion protein bound to Trk A and inhibited NGF-induced autophosphorylation in vitro. Furthermore, the in vivo kinetics of the inhibition of Trk A tyrosine kinase activity by caveolin expression correlated with an increased ability of NGF to induce sphingomyelin hydrolysis through p75NTR. In summary, our results suggest that the interaction of caveolin with neurotrophin receptors may have functional consequences in regulating signaling through p75NTR and Trk A in neuronal and glial cell populations. nerve growth factor caveolin-enriched membrane detergent-insoluble glycosphingolipid-enriched domain noncaveolar membrane glutathione S-transferase protein A-Sepharose phosphate-buffered saline polyacrylamide gel electrophoresis sphingomyelin immunoprecipitation. Neurotrophins are a family of growth factors that mediate the survival, development, and death of specific populations of neurons and glial cells (1Glass D.J. Yancopoulos G.D. Trends Cell Biol. 1993; 3: 262-268Abstract Full Text PDF PubMed Scopus (155) Google Scholar). Many of the classic trophic signals elicited by neurotrophins (nerve growth factor (NGF),1 brain-derived neurotrophic factor, and neurotrophin-3) require the presence of a specific member of the Trk tyrosine kinase receptor family (Trk A, Trk B, and Trk C, respectively (2Cordon-Cardo C. Tapley P. Jing S. Nanduri V. O'Rourke E. Lamballe F. Kovary K. Klein R. Jones K.R. Reichardt L.F. Barbacid M. Cell. 1991; 66: 173-183Abstract Full Text PDF PubMed Scopus (436) Google Scholar, 3Glass D.J. Nye S.H. Hantzpoulos P. Macchi M.J. Squinto S.P. Goldfard M. Yancopoulos G.D. Cell. 1991; 66: 405-413Abstract Full Text PDF PubMed Scopus (240) Google Scholar, 4Klein R. Jing S. Nanduri V. O'Rourke E. Barbacid M. Cell. 1991; 65: 189-197Abstract Full Text PDF PubMed Scopus (1138) Google Scholar, 5Kaplan D.R. Martin-Zanca D. Chao M.V. Parada L.F. Science. 1991; 252: 554-558Crossref PubMed Scopus (1135) Google Scholar, 6Lamballe F. Klein R. Barbacid M. Cell. 1991; 66: 967-979Abstract Full Text PDF PubMed Scopus (913) Google Scholar, 7Lamballe F. Tapley P. Barbacid M. EMBO J. 1993; 12: 3083-3094Crossref PubMed Scopus (149) Google Scholar, 8Klein R. Nanduri V. Jing S. Lamballe F. Tapley P. Bryant S. Cordon-Cardo C. Jones K.R. Reichardt L.F. Barbacid M. Cell. 1991; 66: 395-403Abstract Full Text PDF PubMed Scopus (770) Google Scholar)). After neurotrophin binding, Trk receptors undergo dimerization and transphosphorylation on specific tyrosine residues, a requisite step for activation of their tyrosine kinase activity and to signaling S. Tapley P. Barbacid M. Full Text PDF PubMed Scopus Google Scholar, D.R. J. PubMed Scopus Google Scholar). In death signals P. Chao M.V. PubMed Scopus Google Scholar, PubMed Scopus Google may be in specific cell through the interaction of NGF with a protein the low-affinity neurotrophin p75NTR S. Trends Full Text Full Text PDF PubMed Scopus Google Scholar, D.R. Cell Biol. PubMed Scopus Google Scholar). The of p75NTR may be by of the P. Chao M.V. PubMed Scopus Google that from the hydrolysis of sphingomyelin Chao M.V. Science. PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google in neurotrophin signaling that interactions between Trk and p75NTR signaling can to neurotrophins D.R. Cell Biol. PubMed Scopus Google Scholar). that p75NTR can D.R. Cell Biol. PubMed Scopus Google Scholar, D. M. Chao M.V. D.J. Full Text PDF Scopus Google Scholar, R. 1993; Full Text PDF PubMed Scopus Google Scholar, M.V. J. Scopus Google the of Trk in regulating p75NTR-dependent signaling by and brain-derived neurotrophic factor and hydrolysis in PC12 cells, Trk Trk NGF was J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). the inhibition of Trk A tyrosine kinase activity with NGF to the that Trk A activation can inhibit of p75NTR functional to the of neurotrophins on cell by M. D.J. R. J. J. Cell Biol. PubMed Scopus Google that Trk A activation inhibited brain-derived neurotrophic p75NTR-dependent death of Science. PubMed Scopus Google that expression of Trk A was to the of p75NTR in and expression of Trk A in inhibited NGF-induced p75NTR-dependent and the of protein P. Chao M.V. J. PubMed Google Scholar). suggest that factors that Trk tyrosine kinase activity be to modulate interactions between neurotrophin signaling a protein that a that may the activity of cell growth pathways. a member of a family that and and a protein in the of caveolae J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Cell Biol. PubMed Scopus Google for our of caveolin be with are of the membrane that are in the of and are also localized for signal J. Biol. Full Text Full Text PDF PubMed Scopus Google through tyrosine kinase receptors C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. P. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, P. J. Biol. Full Text Full Text PDF PubMed Scopus Google J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, P. J. Biol. Full Text Full Text PDF PubMed Scopus Google and signaling J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. Cell. PubMed Scopus Google Scholar). cells membrane a with caveolae can with S. M. M. S.H. J. Biol. Full Text Full Text PDF PubMed Scopus Google S. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google protein kinase M. C. J. S. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google S. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google R. J. Biol. Full Text Full Text PDF PubMed Scopus Google and tyrosine kinase receptors J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google through direct the interaction of with caveolin functional consequences on signaling because caveolin can inhibit the activity of R. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, R. J. Biol. Full Text Full Text PDF PubMed Scopus Google protein kinase M. C. J. S. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google and tyrosine J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). that the interaction of caveolin with Trk may also have functional consequences on regulating between the Trk A and pathways. We that of caveolin in PC12 cells and Trk A autophosphorylation in to Trk A with and interaction NGF-induced autophosphorylation of Trk to inhibition of Trk A J. Biol. Full Text Full Text PDF PubMed Scopus Google caveolin inhibition of Trk A signaling NGF to induce hydrolysis through p75NTR. the that caveolin may signaling through Trk and p75NTR receptors in specific neuronal have that caveolin can interact with p75NTR and Trk A, and that interaction may neurotrophin In Trk A co-immunoprecipitated with caveolin in Trk A-PC12 cells that were transfected with Trk A also bound and with a fusion protein the of Caveolin expression in activation of Trk A tyrosine kinase activity that the NGF-induced of PC12 cells transfected with Furthermore, have that caveolin can directly NGF-induced Trk A autophosphorylation in vitro. our that the of caveolin expression on NGF-induced may be due to in the magnitude and duration of receptor autophosphorylation through a direct and interaction of caveolin with Trk of NGF-induced in cells be by in the of Trk A from the cells, because Trk A were because in vivo autophosphorylation of Trk A in the cells, that caveolin the of NGF to Trk the that caveolin may with the of Trk A to in activation in S. Tapley P. Barbacid M. Full Text PDF PubMed Scopus Google Scholar). the in caveolin may tyrosine that Trk the ability of the fusion protein to the activation of Trk A suggest that a tyrosine for the inhibition of receptor that caveolin inhibited growth factor receptor through a direct interaction of an of caveolin domain with the growth factor receptor domain J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google have that domain of caveolin with a specific caveolin domain in the kinase domain of tyrosine Trk were to a interaction between Trk A and a caveolin fusion protein the domain of caveolin of the Trk A bound to the fusion protein in to a to tyrosine kinase receptors a in caveolin domain J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google may in caveolin with receptors and kinase the of the interaction of caveolin with tyrosine kinase receptors by the of the growth factor receptor and the receptor with the interaction of of receptors with caveolin by the interaction of caveolin domain with domain of caveolin growth factor receptor kinase activity J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google receptor kinase activity M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Trk A, was found to interact with caveolin through domain that the domain of p75NTR be a to that were caveolin 1993; PubMed Scopus Google a that may be for a of was unable to the of p75NTR to caveolin that p75NTR may the interaction of receptor with domain of caveolin p75NTR and Trk receptors may interact with of that of neurotrophin receptors may to the of C. S. J. Biol. Full Text Full Text PDF PubMed Scopus Google and that caveolin and are expressed in specific neuronal populations J. Scopus Google Scholar, R. J. PubMed Google that the interactions of may be to neurotrophin signaling pathways. to the inhibition of Trk A with caveolin expression the inhibition of p75NTR In the of cells hydrolysis with NGF This was the a of Trk A activation in This that Trk A activation may hydrolysis in cells, and that in can the ability of Trk A to inhibit p75NTR results the that caveolin may be an of between tyrosine kinase and signaling to Trk receptors and to that that an between caveolin J. Scopus Google Scholar, R. J. PubMed Google and Trk A M. J. Scopus Google in cells of the the of the inhibition of Trk A by caveolin may a for the interaction of caveolin with Trk family was was that PC12 cells may caveolin and that caveolin expression NGF-induced of PC12 cells F. D. M. M. S. PubMed Scopus Google Scholar). In with were to caveolin in PC12 cells, an the of caveolin results with our because PC12 cells caveolin and caveolin Trk A tyrosine kinase PC12 cells undergo in to that F. D. M. M. S. PubMed Scopus Google that caveolin expression was by of the NGF-induced of PC12 We an of magnitude by of caveolin in PC12 cells results be with the that increased expression of caveolin in neurons may to signals from Trk the of in PC12 cells to that caveolin in PC12 cells may Trk A to to to the signaling in D.R. Cell Biol. PubMed Scopus Google Scholar). in cells, caveolin may be to with the Trk A activation by NGF caveolin the of the interaction of caveolin with Trk A may suggest that interaction a of Trk A by NGF that may be to This be with the for NGF activation of Trk A for the of PC12 cells S.H. PubMed Scopus Google summary, the an for the interactions between and receptors This from signaling in that receptor can signal in in to and direct interactions a of and The interaction of receptors with a protein that and the activity of signaling an of to interactions may have in neurotrophin in specific cell regulating the of receptor may the activation of tyrosine kinase and the the interactions between the and tyrosine kinase signaling and their consequences a and of cell Neurotrophins are a family of growth factors that mediate the survival, development, and death of specific populations of neurons and glial cells (1Glass D.J. Yancopoulos G.D. Trends Cell Biol. 1993; 3: 262-268Abstract Full Text PDF PubMed Scopus (155) Google Scholar). Many of the classic trophic signals elicited by neurotrophins (nerve growth factor (NGF),1 brain-derived neurotrophic factor, and neurotrophin-3) require the presence of a specific member of the Trk tyrosine kinase receptor family (Trk A, Trk B, and Trk C, respectively (2Cordon-Cardo C. Tapley P. Jing S. Nanduri V. O'Rourke E. Lamballe F. Kovary K. Klein R. Jones K.R. Reichardt L.F. Barbacid M. Cell. 1991; 66: 173-183Abstract Full Text PDF PubMed Scopus (436) Google Scholar, 3Glass D.J. Nye S.H. Hantzpoulos P. Macchi M.J. Squinto S.P. Goldfard M. Yancopoulos G.D. Cell. 1991; 66: 405-413Abstract Full Text PDF PubMed Scopus (240) Google Scholar, 4Klein R. Jing S. Nanduri V. O'Rourke E. Barbacid M. Cell. 1991; 65: 189-197Abstract Full Text PDF PubMed Scopus (1138) Google Scholar, 5Kaplan D.R. Martin-Zanca D. Chao M.V. Parada L.F. Science. 1991; 252: 554-558Crossref PubMed Scopus (1135) Google Scholar, 6Lamballe F. Klein R. Barbacid M. Cell. 1991; 66: 967-979Abstract Full Text PDF PubMed Scopus (913) Google Scholar, 7Lamballe F. Tapley P. Barbacid M. EMBO J. 1993; 12: 3083-3094Crossref PubMed Scopus (149) Google Scholar, 8Klein R. Nanduri V. Jing S. Lamballe F. Tapley P. Bryant S. Cordon-Cardo C. Jones K.R. Reichardt L.F. Barbacid M. Cell. 1991; 66: 395-403Abstract Full Text PDF PubMed Scopus (770) Google Scholar)). After neurotrophin binding, Trk receptors undergo dimerization and transphosphorylation on specific tyrosine residues, a requisite step for activation of their tyrosine kinase activity and to signaling S. Tapley P. Barbacid M. Full Text PDF PubMed Scopus Google Scholar, D.R. J. PubMed Scopus Google Scholar). In death signals P. Chao M.V. PubMed Scopus Google Scholar, PubMed Scopus Google may be in specific cell through the interaction of NGF with a protein the low-affinity neurotrophin p75NTR S. Trends Full Text Full Text PDF PubMed Scopus Google Scholar, D.R. Cell Biol. PubMed Scopus Google Scholar). The of p75NTR may be by of the P. Chao M.V. PubMed Scopus Google that from the hydrolysis of sphingomyelin Chao M.V. Science. PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). in neurotrophin signaling that interactions between Trk and p75NTR signaling can to neurotrophins D.R. Cell Biol. PubMed Scopus Google Scholar). that p75NTR can D.R. Cell Biol. PubMed Scopus Google Scholar, D. M. Chao M.V. D.J. Full Text PDF Scopus Google Scholar, R. 1993; Full Text PDF PubMed Scopus Google Scholar, M.V. J. Scopus Google the of Trk in regulating p75NTR-dependent signaling by and brain-derived neurotrophic factor and hydrolysis in PC12 cells, Trk Trk NGF was J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). the inhibition of Trk A tyrosine kinase activity with NGF to the that Trk A activation can inhibit of p75NTR functional to the of neurotrophins on cell by M. D.J. R. J. J. Cell Biol. PubMed Scopus Google that Trk A activation inhibited brain-derived neurotrophic p75NTR-dependent death of Science. PubMed Scopus Google that expression of Trk A was to the of p75NTR in and expression of Trk A in inhibited NGF-induced p75NTR-dependent and the of protein P. Chao M.V. J. PubMed Google Scholar). suggest that factors that Trk tyrosine kinase activity be to modulate interactions between neurotrophin signaling pathways. a protein that a that may the activity of cell growth pathways. a member of a family that and and a protein in the of caveolae J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Cell Biol. PubMed Scopus Google for our of caveolin be with are of the membrane that are in the of and are also localized for signal J. Biol. Full Text Full Text PDF PubMed Scopus Google through tyrosine kinase receptors C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. P. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, P. J. Biol. Full Text Full Text PDF PubMed Scopus Google J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, P. J. Biol. Full Text Full Text PDF PubMed Scopus Google and signaling J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. Cell. PubMed Scopus Google Scholar). cells membrane a with caveolae Caveolin can with S. M. M. S.H. J. Biol. Full Text Full Text PDF PubMed Scopus Google S. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google protein kinase M. C. J. S. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google S. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google R. J. Biol. Full Text Full Text PDF PubMed Scopus Google and tyrosine kinase receptors J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google through direct the interaction of with caveolin functional consequences on signaling because caveolin can inhibit the activity of R. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, R. J. Biol. Full Text Full Text PDF PubMed Scopus Google protein kinase M. C. J. S. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google and tyrosine J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). that the interaction of caveolin with Trk may also have functional consequences on regulating between the Trk A and pathways. We that of caveolin in PC12 cells and Trk A autophosphorylation in to Trk A with and interaction NGF-induced autophosphorylation of Trk to inhibition of Trk A J. Biol. Full Text Full Text PDF PubMed Scopus Google caveolin inhibition of Trk A signaling NGF to induce hydrolysis through p75NTR. the that caveolin may signaling through Trk and p75NTR receptors in specific neuronal populations. have that caveolin can interact with p75NTR and Trk A, and that interaction may neurotrophin In Trk A co-immunoprecipitated with caveolin in Trk A-PC12 cells that were transfected with Trk A also bound and with a fusion protein the of Caveolin expression in activation of Trk A tyrosine kinase activity that the NGF-induced of PC12 cells transfected with Furthermore, have that caveolin can directly NGF-induced Trk A autophosphorylation in vitro. our that the of caveolin expression on NGF-induced may be due to in the magnitude and duration of receptor autophosphorylation through a direct and interaction of caveolin with Trk of NGF-induced in cells be by in the of Trk A from the cells, because Trk A were because in vivo autophosphorylation of Trk A in the cells, that caveolin the of NGF to Trk the that caveolin may with the of Trk A to in activation in S. Tapley P. Barbacid M. Full Text PDF PubMed Scopus Google Scholar). the in caveolin may tyrosine that Trk the ability of the fusion protein to the activation of Trk A suggest that a tyrosine for the inhibition of receptor that caveolin inhibited growth factor receptor through a direct interaction of an of caveolin domain with the growth factor receptor domain J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google have that domain of caveolin with a specific caveolin domain in the kinase domain of tyrosine Trk were to a interaction between Trk A and a caveolin fusion protein the domain of caveolin of the Trk A bound to the fusion protein in to a to tyrosine kinase receptors a in caveolin domain J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google may in caveolin with receptors and kinase the of the interaction of caveolin with tyrosine kinase receptors by the of the growth factor receptor and the receptor with the interaction of of receptors with caveolin by the interaction of caveolin domain with domain of caveolin growth factor receptor kinase activity J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google receptor kinase activity M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Trk A, was found to interact with caveolin through domain that the domain of p75NTR be a to that were caveolin 1993; PubMed Scopus Google a that may be for a of was unable to the of p75NTR to caveolin that p75NTR may the interaction of receptor with domain of caveolin p75NTR and Trk receptors may interact with of that of neurotrophin receptors may to the of C. S. J. Biol. Full Text Full Text PDF PubMed Scopus Google and that caveolin and are expressed in specific neuronal populations J. Scopus Google Scholar, R. J. PubMed Google that the interactions of may be to neurotrophin signaling pathways. to the inhibition of Trk A with caveolin expression the inhibition of p75NTR In the of cells hydrolysis with NGF This was the a of Trk A activation in This that Trk A activation may hydrolysis in cells, and that in can the ability of Trk A to inhibit p75NTR results the that caveolin may be an of between tyrosine kinase and signaling to Trk receptors and to that that an between caveolin J. Scopus Google Scholar, R. J. PubMed Google and Trk A M. J. Scopus Google in cells of the the of the inhibition of Trk A by caveolin may a for the interaction of caveolin with Trk family was was that PC12 cells may caveolin and that caveolin expression NGF-induced of PC12 cells F. D. M. M. S. PubMed Scopus Google Scholar). In with were to caveolin in PC12 cells, an the of caveolin results with our because PC12 cells caveolin and caveolin Trk A tyrosine kinase PC12 cells undergo in to that F. D. M. M. S. PubMed Scopus Google that caveolin expression was by of the NGF-induced of PC12 We an of magnitude by of caveolin in PC12 cells results be with the that increased expression of caveolin in neurons may to signals from Trk the of in PC12 cells to that caveolin in PC12 cells may Trk A to to to the signaling in D.R. Cell Biol. PubMed Scopus Google Scholar). in cells, caveolin may be to with the Trk A activation by NGF caveolin the of the interaction of caveolin with Trk A may suggest that interaction a of Trk A by NGF that may be to This be with the for NGF activation of Trk A for the of PC12 cells S.H. PubMed Scopus Google summary, the an for the interactions between and receptors This from signaling in that receptor can signal in in to and direct interactions a of and The interaction of receptors with a protein that and the activity of signaling an of to interactions may have in neurotrophin in specific cell regulating the of receptor may the activation of tyrosine kinase and the the interactions between the and tyrosine kinase signaling and their consequences a and of cell We have that caveolin can interact with p75NTR and Trk A, and that interaction may neurotrophin In Trk A co-immunoprecipitated with caveolin in Trk A-PC12 cells that were transfected with Trk A also bound and with a fusion protein the of Caveolin expression in activation of Trk A tyrosine kinase activity that the NGF-induced of PC12 cells transfected with Furthermore, have that caveolin can directly NGF-induced Trk A autophosphorylation in vitro. our that the of caveolin expression on NGF-induced may be due to in the magnitude and duration of receptor autophosphorylation through a direct and interaction of caveolin with Trk The of NGF-induced in cells be by in the of Trk A from the cells, because Trk A were because in vivo autophosphorylation of Trk A in the cells, that caveolin the of NGF to Trk the that caveolin may with the of Trk A to in activation in S. Tapley P. Barbacid M. Full Text PDF PubMed Scopus Google Scholar). the in caveolin may tyrosine that Trk the ability of the fusion protein to the activation of Trk A suggest that a tyrosine for the inhibition of receptor A that caveolin inhibited growth factor receptor through a direct interaction of an of caveolin domain with the growth factor receptor domain J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google have that domain of caveolin with a specific caveolin domain in the kinase domain of tyrosine Trk were to a interaction between Trk A and a caveolin fusion protein the domain of caveolin of the Trk A bound to the fusion protein in to a to tyrosine kinase receptors a in caveolin domain J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google may in caveolin with receptors and kinase the of the interaction of caveolin with tyrosine kinase receptors by the of the growth factor receptor and the receptor with the interaction of of receptors with caveolin by the interaction of caveolin domain with domain of caveolin growth factor receptor kinase activity J. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google receptor kinase activity M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). Trk A, was found to interact with caveolin through domain that the domain of p75NTR be a to that were caveolin 1993; PubMed Scopus Google a that may be for a of was unable to the of p75NTR to caveolin that p75NTR may the interaction of receptor with domain of caveolin p75NTR and Trk receptors may interact with of The that of neurotrophin receptors may to the of C. S. J. Biol. Full Text Full Text PDF PubMed Scopus Google and that caveolin and are expressed in specific neuronal populations J. Scopus Google Scholar, R. J. PubMed Google that the interactions of may be to neurotrophin signaling pathways. to the inhibition of Trk A with caveolin expression the inhibition of p75NTR In the of cells hydrolysis with NGF This was the a of Trk A activation in This that Trk A activation may hydrolysis in cells, and that in can the ability of Trk A to inhibit p75NTR results the that caveolin may be an of between tyrosine kinase and signaling to Trk receptors and to that that an between caveolin J. Scopus Google Scholar, R. J. PubMed Google and Trk A M. J. Scopus Google in cells of the the of the inhibition of Trk A by caveolin may a for the interaction of caveolin with Trk family was was that PC12 cells may caveolin and that caveolin expression NGF-induced of PC12 cells F. D. M. M. S. PubMed Scopus Google Scholar). In with were to caveolin in PC12 cells, an the of caveolin results with our because PC12 cells caveolin and caveolin Trk A tyrosine kinase PC12 cells undergo in to that F. D. M. M. S. PubMed Scopus Google that caveolin expression was by of the NGF-induced of PC12 We an of magnitude by of caveolin in PC12 cells results be with the that increased expression of caveolin in neurons may to signals from Trk the of in PC12 cells to that caveolin in PC12 cells may Trk A to to to the signaling in D.R. Cell Biol. PubMed Scopus Google Scholar). in cells, caveolin may be to with the Trk A activation by NGF caveolin the of the interaction of caveolin with Trk A may suggest that interaction a of Trk A by NGF that may be to This be with the for NGF activation of Trk A for the of PC12 cells S.H. PubMed Scopus Google Scholar). In summary, the an for the interactions between and receptors This from signaling in that receptor can signal in in to and direct interactions a of and The interaction of receptors with a protein that and the activity of signaling an of to interactions may have in neurotrophin in specific cell regulating the of receptor may the activation of tyrosine kinase and the the interactions between the and tyrosine kinase signaling and their consequences a and of cell We for A-PC12 cells and for of the
Bilderback et al. (Fri,) studied this question.