The role of Tyro 3 subfamily receptors in the regulation of hemostasis and megakaryocytopoiesis.
OBJECTIVE
The molecular mechanisms regulating megakaryocytopoiesis and hemostasis remain largely unknown. The Tyro 3 subfamily of receptor tyrosine kinases (RTK), which is composed of three members (Tyro 3, Axl and Mer), plays important roles in various tissues, such as those in the nervous, immune and reproductive systems. Here, we investigate the roles of the Tyro 3 RTK subfamily in regulating megakaryocytopoiesis and hemostasis.


METHODS
Single, double, and triple knock-out mice for the three Tyro 3 RTK were used in the study. Bleeding time, platelet count, megakaryocyte count, megakaryocyte ploidy, rate of proplatelet formation, platelet aggregation and ATP release were used as criteria to evaluate hemostasis, megakaryocytopoiesis and platelet function.


RESULTS
Mice lacking all three receptors had impaired hemostasis and mild thrombocytopenia, which may be due to platelet dysfunction and defective megakaryocytopoiesis. Mice lacking different combinations of two receptors of the Tyro 3 RTK subfamily had normal platelet counts in peripheral blood, but exhibited impaired hemostasis and platelet function. Although knock-out mice for any single receptor had normal hemostasis and megakaryocytopoiesis, they exhibited a mild platelet dysfunction.


CONCLUSIONS
The Tyro 3 RTK subfamily plays important roles in regulating hemostasis, megakaryocytopoiesis and platelet function.
Wang
Haikun
H
Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Chen
Song
S
Chen
Yongmei
Y
Wang
Huizhen
H
Wu
Hui
H
Tang
Hongmei
H
Xiong
Weipeng
W
Ma
Jing
J
Ge
Yehua
Y
Lu
Qingxian
Q
Han
Daishu
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006474:Hemorrhagic Disorders / Q000235:genetics*; D006487:Hemostasis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010974:Platelet Aggregation; D010976:Platelet Count; D011003:Ploidies; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology; D013921:Thrombocytopenia / Q000235:genetics*; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase
D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D000255:Adenosine Triphosphate; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; C513478:Tyro3 protein, mouse; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; C000722290:AXL receptor tyrosine kinase, mouse