Cleavage and release of a soluble form of the receptor tyrosine kinase ARK in vitro and in vivo.
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 of 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.
Costa
M
M
Department of Microbiology and Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA.
Bellosta
P
P
Basilico
C
C
D016475:3T3 Cells; D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins; D016716:PC12 Cells; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012995:Solubility; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6