During the development of the peripheral nervous system, Schwann cells, the myelin-forming glia, migrate along axons before initiating myelination. We previously demonstrated that endogenous neurotrophin-3 (NT3) acting through the TrkC tyrosine kinase receptor enhances migration of premyelinating Schwann cells. This signaling pathway is mediated by the c-Jun N-terminal kinase (JNK) cascade regulated by the Rho GTPases Rac1 and Cdc42. However, missing is the link between TrkC and the GTPases. Here, we show that a guanine-nucleotide exchange factor (GEF), Dbl's big sister (Dbs), couples with TrkC to activate Cdc42 in Schwann cells. Furthermore, TrkC directly phosphorylates Dbs, thereby inducing the Cdc42-GEF activity. Taken together, activation of TrkC triggers Schwann cell migration by regulating Dbs upon direct tyrosine phosphorylation, providing a mechanism whereby a membrane receptor tyrosine kinase can induce the activation of Rho GTPase-GEFs.
机构:Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
Aghazadeh, B
;
Lowry, WE
论文数: 0引用数: 0
h-index: 0
机构:Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
Lowry, WE
;
Huang, XY
论文数: 0引用数: 0
h-index: 0
机构:Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
Huang, XY
;
Rosen, MK
论文数: 0引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Cheng, L
;
Mahon, GM
论文数: 0引用数: 0
h-index: 0
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Mahon, GM
;
Kostenko, EV
论文数: 0引用数: 0
h-index: 0
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Kostenko, EV
;
Whitehead, IP
论文数: 0引用数: 0
h-index: 0
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
机构:
Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA
Huang, EJ
;
Reichardt, LF
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA
机构:Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
Aghazadeh, B
;
Lowry, WE
论文数: 0引用数: 0
h-index: 0
机构:Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
Lowry, WE
;
Huang, XY
论文数: 0引用数: 0
h-index: 0
机构:Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
Huang, XY
;
Rosen, MK
论文数: 0引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Cheng, L
;
Mahon, GM
论文数: 0引用数: 0
h-index: 0
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Mahon, GM
;
Kostenko, EV
论文数: 0引用数: 0
h-index: 0
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Kostenko, EV
;
Whitehead, IP
论文数: 0引用数: 0
h-index: 0
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
机构:
Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA
Huang, EJ
;
Reichardt, LF
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA