Reference - Detail
| RRC ID | 1392 |
|---|---|
| Author | Motegi A, Fujimoto J, Kotani M, Sakuraba H, Yamamoto T. |
| Title | ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth. |
| Journal | J Cell Sci |
| Abstract |
Anaplastic lymphoma kinase (ALK) is a receptor-type protein tyrosine kinase that is expressed preferentially in neurons of the central and peripheral nervous systems at late embryonic stages. To elucidate the role of ALK in neurons, we developed an agonist monoclonal antibody (mAb) against the extracellular domain of ALK. Here we show that mAb16-39 elicits tyrosine phosphorylation of endogenously expressed ALK in human neuroblastoma (SK-N-SH) cells. Stimulation of these cells with mAb16-39 markedly induces the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), Shc, and c-Cbl and also their interaction with ALK and activation of ERK1/2. Furthermore, we show that continuous incubation with mAb16-39 induces the cell growth and neurite outgrowth of SK-N-SH cells. These responses are completely blocked by MEK inhibitor PD98059 but not by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, indicating an essential role of the mitogen-activated protein kinase (MAP kinase) signaling cascade in ALK-mediated growth and differentiation of neurons. |
| Volume | 117(Pt 15) |
| Pages | 3319-29 |
| Published | 2004-7-1 |
| DOI | 10.1242/jcs.01183 |
| PII | 117/15/3319 |
| PMID | 15226403 |
| MeSH | Adaptor Proteins, Signal Transducing / metabolism Anaplastic Lymphoma Kinase Animals Antibodies, Monoclonal / chemistry Cell Line Cell Line, Tumor Cell Proliferation DNA / metabolism Dose-Response Relationship, Drug Enzyme Activation Enzyme Inhibitors / pharmacology Enzyme-Linked Immunosorbent Assay Flavonoids / pharmacology Humans Immunoblotting Immunoprecipitation Insulin Receptor Substrate Proteins MAP Kinase Signaling System Mice Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Mitogens / metabolism NIH 3T3 Cells Neuroblastoma / metabolism Neuroblastoma / pathology Neurons / metabolism Neurons / physiology* Phosphoproteins / metabolism Phosphorylation Plasmids / metabolism Protein-Tyrosine Kinases / metabolism Protein-Tyrosine Kinases / physiology* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-cbl Receptor Protein-Tyrosine Kinases Shc Signaling Adaptor Proteins Src Homology 2 Domain-Containing, Transforming Protein 1 Thymidine / metabolism Time Factors Tyrosine / metabolism Ubiquitin-Protein Ligases / metabolism |
| IF | 4.573 |
| Times Cited | 101 |
| WOS Category | CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | SK-N-SH(RCB0426) |