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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #164764
Title: ROLE OF GAS6/AXL SIGNALING IN LENS EPITHELIAL CELL PROLIFERATION AND SURVIVAL

Author
item VALVERDE, PALOMA - TUFTS-HNRCA
item OBIN, MARTIN - TUFTS-HNRCA
item TAYLOR, ALLEN - TUFTS-HNRCA

Submitted to: Experimental Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2003
Publication Date: 1/1/2004
Citation: Valverde, P., Obin, M.S., Taylor, A. 2004. Role of gas6/axl signaling in lens epithelial cell proliferation and survival. Experimental Eye Research. 78:27-37.

Interpretive Summary: Axl is a receptor that is activated by Gas6, a growth factor that belongs to the vitamin K-dependent protein family. Although, when Gas6 binds to Axl it sends signals to a variety of cell types to encourage cell division or discourage cell death, the purpose of the Axl-Gas6 system in normal lens biology is not known. We demonstrate for the first time that Axl protein is found in normal rat and cow lens and Gas6 is present in the solution surrounding the cow eye. We have also detected tyrosine-phosphorylated Axl in the normal rat and cow lens epithelial tissues. A human Gas6 protein produced by genetic engineering is able to act as a growth factor in cultured lens epithelial cells by activating Axl and then the Akt signaling pathway. Gas6 is also responsible for the survival and anti-apoptotic response in human lens epithelial cells subjected to serum-starvation, or transforming growth factor treatment, resulting in decreased DNA condensation, or caspase-3 activity. Taken together, these data suggest that Gas6/Axl signaling plays an important role in the control of lens epithelial cell growth and survival as well as in the maintenance of lens homeostasis.

Technical Abstract: Axl is a receptor tyrosine kinase that is activated by Gas6, a growth factor that belongs to the vitamin K-dependent protein family. Although Gas6 binding to Axl has been shown to transmit mitogenic and/or antiapoptotic signals to a variety of cell types, the role of the Axl-Gas6 system in normal and pathological lens biology is not known.We demonstrate for the first time that Axl protein is expressed in normal rat and bovine lens and that its ligand, Gas6, is present in bovine aqueous humor. In addition, we have detected tyrosine-phosphorylated Axl in normal rat and bovine lens epithelial tissues. We further show that human recombinant Gas6 is able to act as a growth factor in cultured human lens epithelial cells by activating Axl and then the AKT signaling pathway. Gas6 mediates a survival and anti-apoptotic response in cultured human lens epithelial cells subjected to serum-starvation (48-72hr), or treated with transforming growth factor beta1 (5 ng ml(-1), 48hr) or tumor necrosis alpha (100 ng ml(-1), 48hr), as demonstrated by increased number of viable cells, and decreased DNA condensation or caspase-3 activity. In contrast, Gas6 is not able to block apoptosis induced by staurosporin (1microM, 5-24hr) in human lens epithelial cells. Taken together, these data suggest that the Gas6/Axl signaling plays an important role in the control of lens epithelial cell growth and survival and hence in the maintenance of lens homeostasis.