TY - JOUR
T1 - Priming of the vascular endothelial growth factor signaling pathway by thrombospondin-1, CD36, and spleen tyrosine kinase
AU - Kazerounian, Shideh
AU - Duquette, Mark
AU - Reyes, Millys A.
AU - Lawler, James T.
AU - Song, Keli
AU - Perruzzi, Carole
AU - Primo, Luca
AU - Khosravi-Far, Roya
AU - Bussolino, Federico
AU - Rabinovitz, Isaac
AU - Lawler, Jack
PY - 2011/4/28
Y1 - 2011/4/28
N2 - CD36 plays a critical role in the inhibition of angiogenesis through binding to the type 1 repeats of thrombospondin-1 (TSP-1) and activating Fyn tyrosine kinase and MAPK pathways. Here, we reveal a novel association of CD36 with VEGFR-2 and spleen tyrosine kinase (Syk). We also address the correlation between the expression of CD36 and Syk by demonstrating that overexpression of CD36 in HUVECs up-regulates endogenous Syk expression. We also define a new role for TSP-1 and CD36 in the activation of the VEGFR-2 signaling pathway that requires Syk. Our findings also identify a role for Syk as a stimulator of VEGF-A-induced angiogenesis by increasing phosphorylation of Y1175 in VEGFR-2, which is a major tyrosine for promoting VEGF-A-induced endothelial cell migration. Together, these studies introduce a new signaling pathway for TSP-1, CD36, and Syk, and address the role of these proteins in regulating the angiogenic switch.
AB - CD36 plays a critical role in the inhibition of angiogenesis through binding to the type 1 repeats of thrombospondin-1 (TSP-1) and activating Fyn tyrosine kinase and MAPK pathways. Here, we reveal a novel association of CD36 with VEGFR-2 and spleen tyrosine kinase (Syk). We also address the correlation between the expression of CD36 and Syk by demonstrating that overexpression of CD36 in HUVECs up-regulates endogenous Syk expression. We also define a new role for TSP-1 and CD36 in the activation of the VEGFR-2 signaling pathway that requires Syk. Our findings also identify a role for Syk as a stimulator of VEGF-A-induced angiogenesis by increasing phosphorylation of Y1175 in VEGFR-2, which is a major tyrosine for promoting VEGF-A-induced endothelial cell migration. Together, these studies introduce a new signaling pathway for TSP-1, CD36, and Syk, and address the role of these proteins in regulating the angiogenic switch.
UR - http://www.scopus.com/inward/record.url?scp=79955965433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955965433&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-09-305284
DO - 10.1182/blood-2010-09-305284
M3 - Article
C2 - 21378271
AN - SCOPUS:79955965433
VL - 117
SP - 4658
EP - 4666
JO - Blood
JF - Blood
SN - 0006-4971
IS - 17
ER -