Loss of cell adhesion impairs the early response of TrkA to nerve growth factor (NGF).
Within the in vitro model of nerve growth factor (NGF)-dependent differentiation of PC12 cells, loss of adhesion is known to interfere with certain neurotrophic responses and not with others. The present analysis of early NGF signaling shows that the upstream activation of TrkA, as well as the recruitment of the adaptor protein Shc, are dramatically attenuated upon loss of cell adhesion, while the downstream activation of ERK1/2 is unaffected. That loss of cell adhesion interferes with the primary signaling response to NGF (i.e. autophosphorylation of TrkA) may explain why suspended PC12 cells fail to morphologically differentiate in response to NGF. The possibility that established adhesion-driven mechanisms underlie the full responsiveness of TrkA to NGF is discussed.
Gatti
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Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, 10016, USA.
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D020917:Receptor, trkA
D002352:Carrier Proteins; D008565:Membrane Proteins; D020932:Nerve Growth Factor; D020917:Receptor, trkA