An inward rectifier K+ current modulates in neuroblastoma cells the tyrosine phosphorylation of the pp125FAK and associated proteins: role in neuritogenesis.
The relationships between the integrin-mediated activation of inward rectifyier K+ channels (KIR), the phosphorylation of pp125FAK and the rescue of neuritogenesis were studied in 41A3 mouse neuroblastoma cells. Neuritogenesis, elicited by adhesion to FN-enriched substrata, was reversibly impaired by pretreating these cells with the tyrosine kinase inhibitor Herbimycin A. This impairment mimicked that operated by Cs+ ions, which selectively inhibited the integrin-mediated activation of KIR channels. Various phosphotyrosine containing cellular proteins underwent a marked increase upon cell adhesion to FN-coated dishes. This increase was significantly reduced by Cs+ addition. Immunoprecipitation of pp125FAK revealed that the phosphorylation of this kinase and several associated proteins was significantly and reversibly inhibited by Cs+, indicating that integrin-mediated activation of KIR channels is a limiting step upstream to the phosphorylation of pp125FAK in the commitment to neuritogenesis.
Bianchi
L
L
Institute of General Pathology, University of Florence, Firenze, Italy.
Arcangeli
A
A
Bartolini
P
P
Mugnai
G
G
Wanke
E
E
Olivotto
M
M
D000818:Animals; D016227:Benzoquinones; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D047029:Lactams, Macrocyclic; D008564:Membrane Potentials; D051379:Mice; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009447:Neuroblastoma; D018408:Patch-Clamp Techniques; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011972:Receptor, Insulin / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D016227:Benzoquinones; D015815:Cell Adhesion Molecules; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011809:Quinones; D017828:Rifabutin; D019000:Phosphotyrosine; D014443:Tyrosine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse