Integrin α _v β ₃ is a pleiotrophin receptor required for pleiotrophin‐induced endothelial cell migration through receptor protein tyrosine phosphatase β/ζ

Abstract

We have previously shown that the angiogenic growth factor pleiotrophin (PTN) induces migration of endothelial cells through binding to its receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta). In this study, we show that a monoclonal antibody against alpha(nu)beta(3) but not alpha(5)beta(1) integrin abolished PTN-induced human endothelial cell migration in a concentration-dependent manner. Integrin alpha(nu)beta(3) was found to directly interact with PTN in an RGD-independent manner, whereas a synthetic peptide corresponding to the specificity loop of the beta(3) integrin extracellular domain ((177)CYDMKTTC(184)) inhibited PTN-alpha(nu)beta(3) interaction and totally abolished PTN-induced endothelial cell migration. Interestingly, alpha(nu)beta(3) was also found to directly interact with RPTPbeta/zeta, and PTN-induced Y773 phosphorylation of beta(3) integrin was dependent on both RPTPbeta/zeta and the downstream c-src kinase activation. Midkine was found to interact with RPTPbeta/zeta, but not with alpha(nu)beta(3), and caused a small but statistically significant decrease in cell migration. In the same line, PTN decreased migration of different glioma cell lines that express RPTPbeta/zeta but do not express alpha(nu)beta(3), while it stimulated migration of U87MG cells that express alpha(nu)beta(3) on their cell membrane. Overexpression or down-regulation of beta(3) stimulated or abolished, respectively, the effect of PTN on cell migration. Collectively, these data suggest that alpha(nu)beta(3) is a key molecule that determines the stimulatory or inhibitory effect of PTN on cell migration.

Receptor-type Protein-tyrosine Phosphatase ζ Is a Functional Receptor for Interleukin-34

“…For example, in contrast to PTP-signaling in U251 cells, PTPsignaling in hematopoietic stem cells leads to their expansion (75). A positive regulatory role of PTP-in proliferation and migration was also reported in some glioblastomas (32,41) that could reflect the role of known PTP-co-receptors, such as the integrins ␤1 (64) and ␤3 (39), in governing these biological responses.…”

CX3CR1-dependent renal macrophage survival promotes Candida control and host survival

“…Cell lysates were centrifuged at 13,200 g for 10 minutes at 4°C, and equal protein amounts from the supernatant were resuspended in SDS loading buffer with 5% β-mercaptoethanol for downstream Western blot analysis. Proteins were analyzed by SDS-PAGE and transferred to Immobilon P membranes, as previously described (44). Blocking was performed by incubating the membranes with TBST containing 5% nonfat dry milk.…”

Functional Receptors and Intracellular Signal Pathways of Midkine (MK) and Pleiotrophin (PTN)

“…53) Unlike MK, PTN interacts with integrin ανβ3, and the binding is cell adhesion motif-RGD independent. 54) A synthetic peptide corresponding to the β3 extracellular domain (177CYDMKTTC184) inhibits PTN-ανβ3 interaction and totally abolishes PTN-induced endothelial cell migration. 54) 3.4.…”

“…54) A synthetic peptide corresponding to the β3 extracellular domain (177CYDMKTTC184) inhibits PTN-ανβ3 interaction and totally abolishes PTN-induced endothelial cell migration. 54) 3.4. Neuroglycan C (NGC) NGC, membrane-bound chondroitin-sulfated proteoglycan, is specifically expressed in the nervous system and promotes neurite outgrowth of neurons in cultures prepared from the fetal rat cerebral cortex.…”

“…53) Integrin ανβ3, a PTN receptor that mediates endothelial cell migration also interacts with RPTPζ. 54) Furthermore, RPTPζ also interacts with ALK on the membrane and negatively modulates ALK activation by dephosphorylating tyrosine on intracellular domain of ALK. 51) This indicates that, in some specific conditions, the MK and PTN receptor may be a multi-molecular complex combined from several receptors mentioned above.…”