TY - JOUR
T1 - The role of TAM family receptors and ligands in the nervous system
T2 - From development to pathobiology
AU - Shafit-Zagardo, Bridget
AU - Gruber, Ross C.
AU - DuBois, Juwen C.
N1 - Funding Information:
We thank Ms. Hillary Guzik in the Analytical Imaging Facility for her help with images, Ms. Xheni Nishu for help with electron microscopy, Dr. Bryan Kaspar for AAV2/9 vectors, and Dr. Cedric Raine for his expert advice on electron microscopy. We are grateful to Dr. Pablo Garcia de Frutos for educating us on the functional differences between total and free ProS1, and guiding us toward appropriate references. We thank Ms. Kathleen O'Guin for her help in establishing the human co-cultures. Aspects of our research reported in this review were funded by the National Multiple Sclerosis Society (Grant # RG5351-A-10 ) and the National Institues of Health (Grant # NS093134 ).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/8
Y1 - 2018/8
N2 - Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K–dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K–dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 −/− and TAM mutant mice models.
AB - Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K–dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K–dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 −/− and TAM mutant mice models.
KW - Axl and Mertk receptor tyrosine kinase family
KW - Gas6
KW - Homeostasis in the nervous system
KW - Inflammation
KW - Myelination
KW - Phagocytosis
KW - ProS1
KW - Tyro3
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U2 - 10.1016/j.pharmthera.2018.03.002
DO - 10.1016/j.pharmthera.2018.03.002
M3 - Review article
C2 - 29514053
AN - SCOPUS:85046104920
SN - 0163-7258
VL - 188
SP - 97
EP - 117
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
ER -
