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Cleavage and release of a soluble form of the receptor tyrosine kinase ARK in vitro and in vivo
Author(s) -
Costa Mario,
Bellosta Paola,
Basilico Claudio
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199609)168:3<737::aid-jcp27>3.0.co;2-u
Subject(s) - gas6 , receptor tyrosine kinase , extracellular , biology , receptor , microbiology and biotechnology , tyrosine kinase , transmembrane protein , cell surface receptor , tyrosine , in vitro , in vivo , biochemistry , genetics
The receptor tyrosine kinase ARK (also called AXL or UFO) is the murine prototype of a small family of receptors with an extracellular domain resembling cell adhesion molecules and a conserved tyrosine kinase domain. ARK is capable of homophilic binding, as well as of binding to GAS6, a secreted member of the class of vitamin K dependent proteins whose expression is up‐regulated in growth‐arrested cells. To gain understanding of the physiological role of ARK signaling, we have investigated the ARK forms which are expressed by cells in culture as well as by mouse organs. We found that ARK is not only expressed as a transmembrane protein, but is also cleaved in the extracellular domain to generate a soluble ARK form of about 65 kDa, which is easily detected in conditioned media of ARK expressing cells, in serum and plasma and in mouse organs. Soluble ARK is also produced by tumor cells in vivo. The function of these molecules could be that of binding GAS6, thereby inhibiting the interaction of this ligand with its cell‐associated receptor, or they could be involved in binding to ARK itself. © 1996 Wiley‐Liss, Inc.