Integrins stimulate phosphorylation of neurofilament NF-M subunit KSP repeats through activation of extracellular regulated-kinases (Erk1/Erk2) in cultured motoneurons and transfected NIH 3T3 cells.
Integrin-mediated interactions of cells with components of the extracellular matrix (ECM) regulate cell survival, cell proliferation, cell differentiation and cell migration through activation of multiple intracellular signal transduction pathways. In this study, we have demonstrated that integrin-matrix interactions promote KSP tail-domain phosphorylation of neurofilament medium molecular weight subunits (NF-M) in cultured rat spinal cord motoneurons and NF-M transfected NIH 3T3 cells. We found that laminin and fibronectin induce NF-M tail-domain phosphorylation in motoneurons and NIH 3T3 cells transfected with NF-M, respectively. This phosphorylation was selectively inhibited by PD98059, a specific MEK1 inhibitor. This suggests that laminin and fibronectin-induced MEK1 activation and the downstream targets Erk1 and Erk2 are involved in NF-M KSP tail-domain phosphorylation. This pathway appears to represent one of the mechanisms whereby integrin-extracellular matrix interactions are involved in phosphorylation of the NF-M KSP tail domain.
Li
B S
BS
Laboratory of Neurochemistry, NINDS, NIH, Bethesda, Maryland, USA.
Daniels
M P
MP
Pant
H C
HC
D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D005353:Fibronectins / Q000494:pharmacology; D016023:Integrins / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D014162:Transfection
D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D016900:Neurofilament Proteins; D020033:Protein Isoforms; C061195:neurofilament protein M; D020928:Mitogen-Activated Protein Kinases