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Identification of Gas6 as a growth factor for human Schwann cells

R Li, J Chen, G Hammonds, H Phillips, M Armanini, P Wood, R Bunge, PJ Godowski, MX Sliwkowski and JP Mather
Journal of Neuroscience 15 March 1996, 16 (6) 2012-2019; https://doi.org/10.1523/JNEUROSCI.16-06-02012.1996
R Li
Genentech, Inc., South San Francisco, California 94080, USA.
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J Chen
Genentech, Inc., South San Francisco, California 94080, USA.
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G Hammonds
Genentech, Inc., South San Francisco, California 94080, USA.
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H Phillips
Genentech, Inc., South San Francisco, California 94080, USA.
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M Armanini
Genentech, Inc., South San Francisco, California 94080, USA.
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P Wood
Genentech, Inc., South San Francisco, California 94080, USA.
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R Bunge
Genentech, Inc., South San Francisco, California 94080, USA.
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PJ Godowski
Genentech, Inc., South San Francisco, California 94080, USA.
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MX Sliwkowski
Genentech, Inc., South San Francisco, California 94080, USA.
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JP Mather
Genentech, Inc., South San Francisco, California 94080, USA.
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Abstract

Schwann cells are one of the principal components of the peripheral nervous system. They play a crucial role in nerve regeneration and can be used clinically in the repair of injured nerves. We have established serum-free, defined culture conditions that rapidly expand adult human Schwann cells without fibroblast growth. We find that Gas6, a ligand for the Axl and Rse/Tyro3 receptor protein tyrosine kinase family, stimulates human Schwann cell growth, increasing both cell number and thymidine incorporation. Gas6 has synergistic effects with the other known human Schwann cell mitogens, heregulin/glial growth factor and forskolin. Addition of Gas6 causes phosphorylation of Axl and Rse/Tyro3 simultaneously and results in ERK-2 activation. A combination of Gas6 with heregulin and forskolin, on a defined background, supports maximal Schwann cell proliferation, while preserving the typical Schwann cell morphology and expression of the Schwann cell markers S-100, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. Gas6 mRNA is present in both spinal motor neurons and large neurons of the dorsal root ganglia, and neural injury has been reported to upregulate Rse/Axl in the schwann cell. This is the first demonstration of a potentially important biological role for the human Gas6/Rse-Axl system.

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The Journal of Neuroscience: 16 (6)
Journal of Neuroscience
Vol. 16, Issue 6
15 Mar 1996
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Identification of Gas6 as a growth factor for human Schwann cells
R Li, J Chen, G Hammonds, H Phillips, M Armanini, P Wood, R Bunge, PJ Godowski, MX Sliwkowski, JP Mather
Journal of Neuroscience 15 March 1996, 16 (6) 2012-2019; DOI: 10.1523/JNEUROSCI.16-06-02012.1996

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Identification of Gas6 as a growth factor for human Schwann cells
R Li, J Chen, G Hammonds, H Phillips, M Armanini, P Wood, R Bunge, PJ Godowski, MX Sliwkowski, JP Mather
Journal of Neuroscience 15 March 1996, 16 (6) 2012-2019; DOI: 10.1523/JNEUROSCI.16-06-02012.1996
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