Jian-Ping Xiong

Publications (2)20.53 Total impact

• Source

  Available from: PubMed Central

  Article: Regulation of alpha5beta1 integrin conformation and function by urokinase receptor binding.

  Ying Wei, Ralf-Peter Czekay, Liliane Robillard, Matthias C Kugler, Feng Zhang, Kevin K Kim, Jian-Ping Xiong, Martin J Humphries, Harold A Chapman
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  ABSTRACT: Urokinase-type plasminogen activator receptors (uPARs), up-regulated during tumor progression, associate with beta1 integrins, localizing urokinase to sites of cell attachment. Binding of uPAR to the beta-propeller of alpha3beta1 empowers vitronectin adhesion by this integrin. How uPAR modifies other beta1 integrins remains unknown. Using recombinant proteins, we found uPAR directly binds alpha5beta1 and rather than blocking, renders fibronectin (Fn) binding by alpha5beta1 Arg-Gly-Asp (RGD) resistant. This resulted from RGD-independent binding of alpha5beta1-uPAR to Fn type III repeats 12-15 in addition to type III repeats 9-11 bound by alpha5beta1. Suppression of endogenous uPAR by small interfering RNA in tumor cells promoted weaker, RGD-sensitive Fn adhesion and altered overall alpha5beta1 conformation. A beta1 peptide (res 224NLDSPEGGF232) that models near the known alpha-chain uPAR-binding region, or a beta1-chain Ser227Ala point mutation, abrogated effects of uPAR on alpha5beta1. Direct binding and regulation of alpha5beta1 by uPAR implies a modified "bent" integrin conformation can function in an alternative activation state with this and possibly other cis-acting membrane ligands.
  The Journal of Cell Biology 02/2005; 168(3):501-11. · 10.26 Impact Factor
• Source

  Available from: jcb.rupress.org

  Article: Regulation of α5β1 integrin conformation and function by urokinase receptor binding

  Ying Wei, Ralf-Peter Czekay, Liliane Robillard, Matthias C. Kugler, Feng Zhang, Kevin K. Kim, Jian-ping Xiong, Martin J. Humphries, Harold A. Chapman
  [show abstract] [hide abstract]
  ABSTRACT: Urokinase-type plasminogen activator receptors (uPARs), up-regulated during tumor progression, associate with β1 integrins, localizing urokinase to sites of cell attachment. Binding of uPAR to the β-propeller of α3β1 empowers vitronectin adhesion by this integrin. How uPAR modifies other β1 integrins remains unknown. Using recombinant proteins, we found uPAR directly binds α5β1 and rather than blocking, renders fibronectin (Fn) binding by α5β1 Arg-Gly-Asp (RGD) resistant. This resulted from RGD-independent binding of α5β1–uPAR to Fn type III repeats 12–15 in addition to type III repeats 9–11 bound by α5β1. Suppression of endogenous uPAR by small interfering RNA in tumor cells promoted weaker, RGD-sensitive Fn adhesion and altered overall α5β1 conformation. A β1 peptide (res 224NLDSPEGGF232) that models near the known α-chain uPAR-binding region, or a β1-chain Ser227Ala point mutation, abrogated effects of uPAR on α5β1. Direct binding and regulation of α5β1 by uPAR implies a modified “bent” integrin conformation can function in an alternative activation state with this and possibly other cis-acting membrane ligands.
  The Journal of Cell Biology 01/2005; 168(3):501-511. · 10.26 Impact Factor