Adhesion or Plasmin Regulates Tyrosine Phosphorylation of a Novel Membrane Glycoprotein p80/gp140/CUB Domain-containing Protein 1 in Epithelia

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Suspension of cultured human foreskin keratinocytes (HKs) with trypsin phosphorylates tyrosine residues on an 80-kDa membrane glycoprotein, p80 (Xia, Y., Gil, S. G., and Carter, W. G. (1996) J. Cell Biol. 132, 727–740). Readhesion dephosphorylates p80. Sequencing of a p80 cDNA established identity to CUB domain-containing protein 1 (CDCP1), a gene elevated in carcinomas. CDCP1/p80 cDNA encodes three extracellular CUB domains, a transmembrane domain, and two putative cytoplasmic Tyr phosphorylation sites. Treatment of adherent HKs with suramin, a heparin analogue, or inhibitors of phosphotyrosine phosphatases (PTPs; vanadate or calpeptin) increases phosphorylation of p80 and a novel 140-kDa membrane glycoprotein, gp140. Phosphorylated gp140 was identified as a trypsin-sensitive precursor to p80. Identity was confirmed by digestion and phosphorylation studies with recombinant gp140-GFP. Plasmin, a serum protease, also converts gp140 to p80, providing biological significance to the cleavage in wounds. Phosphorylation of gp140 and p80 are mediated by Src family kinases at multiple Tyr residues including Tyr734. Dephosphorylation is mediated by PTP(s). Conversion of gp140 to p80 prolongs phosphorylation of p80 in response to suramin and changes in adhesion. This distinguishes gp140 and p80 and explains the relative abundance of phosphorylated p80 in trypsinized HKs. We conclude that phosphorylation of gp140 is dynamic and balanced by Src family kinase and PTPs yielding low equilibrium phosphorylation. We suggest that the balance is altered by conversion of gp140 to p80 and by adhesion, providing a novel transmembrane phosphorylation signal in epithelial wounds. Suspension of cultured human foreskin keratinocytes (HKs) with trypsin phosphorylates tyrosine residues on an 80-kDa membrane glycoprotein, p80 (Xia, Y., Gil, S. G., and Carter, W. G. (1996) J. Cell Biol. 132, 727–740). Readhesion dephosphorylates p80. Sequencing of a p80 cDNA established identity to CUB domain-containing protein 1 (CDCP1), a gene elevated in carcinomas. CDCP1/p80 cDNA encodes three extracellular CUB domains, a transmembrane domain, and two putative cytoplasmic Tyr phosphorylation sites. Treatment of adherent HKs with suramin, a heparin analogue, or inhibitors of phosphotyrosine phosphatases (PTPs; vanadate or calpeptin) increases phosphorylation of p80 and a novel 140-kDa membrane glycoprotein, gp140. Phosphorylated gp140 was identified as a trypsin-sensitive precursor to p80. Identity was confirmed by digestion and phosphorylation studies with recombinant gp140-GFP. Plasmin, a serum protease, also converts gp140 to p80, providing biological significance to the cleavage in wounds. Phosphorylation of gp140 and p80 are mediated by Src family kinases at multiple Tyr residues including Tyr734. Dephosphorylation is mediated by PTP(s). Conversion of gp140 to p80 prolongs phosphorylation of p80 in response to suramin and changes in adhesion. This distinguishes gp140 and p80 and explains the relative abundance of phosphorylated p80 in trypsinized HKs. We conclude that phosphorylation of gp140 is dynamic and balanced by Src family kinase and PTPs yielding low equilibrium phosphorylation. We suggest that the balance is altered by conversion of gp140 to p80 and by adhesion, providing a novel transmembrane phosphorylation signal in epithelial wounds. Wounding of quiescent epidermis activates changes in adhesion and cell signaling resulting in keratinocyte migration, basement membrane (BM) 1The abbreviations used are: BM, basement membrane; Ab, polyclonal antibody; CDCP1, CUB domain-containing protein 1; FAK, focal adhesion kinase; P-FAK, phospho-FAK; P-p80 and P-gp140, phospho-p80 and phospho-gp140, respectively; HK, human keratinocyte; LC MS/MS, liquid chromatography-coupled mass spectrometry/mass spectrometry; NEM, N-ethylmaleimide; mAb, monoclonal antibody; PTP, phosphotyrosine phosphatase; SFK, Src family kinase; WGA, wheat germ agglutinin; HD, hemidesmosome; HPLC, high pressure liquid chromatography; MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight; MS, mass spectrometry; GFP, green fluorescent protein; uPA, urokinase plasminogen activator; uPAR, uPA receptor. repair, and wound closure (1Martin P. Science. 1997; 276: 75-81Crossref PubMed Scopus (3762) Google Scholar, 2Woodley D.T. O'Toole E. Nadelman C.M. Li W. Progress Dermatol. 1999; 33: 1-12Google Scholar, 3Nguyen B.P. Gil S.G. Ryan M.C. Carter W.G. Curr. Opin. Cell Biol. 2000; 12: 554-562Crossref PubMed Scopus (224) Google Scholar). Based on an in vitro model for wound activation, we reported that trypsin detachment of cultured human foreskin keratinocytes (HKs) promotes phosphorylation of tyrosine residues on an 80-kDa membrane glycoprotein (p80) (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google Scholar). Phosphorylated p80 (P-p80) in suspended HKs is dephosphorylated upon readhesion to laminin 5 via integrins α6β4 and α3β1. In work here, we and p80. We to phosphorylated p80 identified in an in vitro (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google in wound epidermis to laminin 5 in the via α6β4 in cell Wounding epidermis and of keratinocytes at the wound B.P. Gil S. J. Y. Carter W.G. J. Cell Biol. PubMed Scopus Google Scholar). keratinocytes via and via also laminin 5 as a and with via B.P. Gil S. J. Y. Carter W.G. J. Cell Biol. PubMed Scopus Google Scholar, B.P. Gil S.G. Carter W.G. J. Biol. 2000; PubMed Scopus Google Scholar, Carter W.G. J. Cell PubMed Scopus Google Scholar). of with laminin 5 transmembrane with with adhesion of HKs to laminin 5 via promotes with adhesion to or B.P. Gil S. J. Y. Carter W.G. J. Cell Biol. PubMed Scopus Google Scholar). of with are by an of the adhesion or on laminin of laminin 5 adhesion and to B.P. Gil S.G. Carter W.G. J. Biol. 2000; PubMed Scopus Google Scholar). Cell with laminin 5 B.P. Gil S.G. Carter W.G. J. Biol. 2000; PubMed Scopus Google or laminin J. Y. J. Biol. 276: PubMed Scopus Google via focal with low phosphorylation of focal adhesion kinase with adhesion on we also that adhesion to was laminin 5 in phosphorylation of p80 (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google Scholar). Dephosphorylation of P-p80 upon adhesion to laminin is to an of the an of of P-p80 upon adhesion, that a is for the Phosphorylated p80 is in of epithelial and of or epithelial cell (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google Scholar). We that phosphorylation and of p80 on laminin 5 cell and in we the of P-p80 HKs and novel novel 140-kDa transmembrane glycoprotein, is identified as the trypsin-sensitive precursor to p80 and extracellular CUB is identified as the of the CUB domain-containing protein 1 gene that is in human and W. P. PubMed Scopus Google is a for S. Y. PubMed Scopus Google and is to a membrane glycoprotein elevated in human PubMed Scopus Google Scholar). phosphorylation of p80 is mediated by Src family on including tyrosine upon detachment of HKs with trypsin or with suramin, a S. J. E. P. P. J. 2000; PubMed Scopus Google Scholar). trypsin conversion of gp140 to p80 is by serum This conversion the of of p80 relative to gp140 in response to detachment or studies suggest for and adhesion in phosphorylation of in wounds. and monoclonal and fluorescent protein and and the and used to the by to and or Plasmin, wheat germ protein and Cell and Cell and in as J. Scopus Google phosphorylation HKs with or inhibitors for at the to with or suramin for and with and for at was by and the was with 1 NEM, and to the in of HKs was as J. Biol. PubMed Scopus Google as was as the of a with and of p80 and gp140 and gp140 HKs as p80 was HKs suspended with to tyrosine phosphorylation of p80 as (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google Scholar). In gp140 was adherent HKs that with suramin to tyrosine phosphorylation of gp140 and p80. HKs with a cell or suspended HKs with a in NEM, and used that and membrane and the for 1 at membrane was with for at and was with for 1 at or protein was with and the was with the by with and with with by and as Sequencing of p80 of p80 was by the the of p80 protein in was to of p80 on by on a and of by matrix-assisted laser desorption mass to mass and by by This p80 and and of by of gp140 was in the mass by and gp140 was to trypsin and the and was in 5 of and by LC with a mass PubMed Scopus Google Scholar). in the in an was by of the three the the protein and a human of resulting by and protein the identified protein at two with and the in a a of the of p80 was used to a of p80 on the of p80 and with used in with with of the was used by with a in two in identified by on a with of was in was the with 1 was and was on of cDNA and cDNA was by and used to a human keratinocyte cDNA on and at for in and with at for and and and in and was and with to was and to for This identified and a p80 and of cDNA was by of three the multiple of an of the cDNA was resulting cDNA a was in at to the of In of gp140 the at the of gp140. the conversion of to was or keratinocytes with keratinocytes in in serum as of the in on the of by in was of the was with of to and the of with serum and in or with or and by or with or or and with a of HKs with and kinase for by or by suramin for in in vanadate and to phosphatases and with with with and gp140 and was with with a with a Phosphorylation and Dephosphorylation of p80 (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google of HKs with trypsin tyrosine phosphorylation of a 80-kDa membrane glycoprotein, p80, and phosphorylation of 1 and readhesion of the suspended HKs laminin 5 via integrins α6β4 and for increases phosphorylation of and dephosphorylates p80 This that phosphorylation of p80 upon trypsin and upon the of p80 upon that by a is the for the of P-p80 (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google Scholar). in the p80 is and dephosphorylated This that of p80 also in adherent HKs as a of changes in or changes in phosphorylation of p80 identity and the that tyrosine phosphorylation of p80. we and p80, tyrosine kinase and that balance phosphorylation of p80, and in phosphorylation. of P-p80 HKs and studies to p80, of P-p80 for HKs suspended with to phosphorylation of p80. P-p80 was by of a of the with to a membrane of P-p80 the on to membrane by and on or and P-p80 was with and with by HPLC, and mass by and This for p80 mass mass mass mass mass for of the the p80 Sequencing of a p80 cDNA a CUB p80 was on the of p80 and used to a cDNA identified a This cDNA was and of the p80 cDNA was in three of including of the p80 and This established that the p80 cDNA encodes of the 80-kDa protein that was and In an was in the p80 cDNA at that that the was an in the p80 cDNA in the cDNA used for and the p80 residues of the identified by a the the and the protein an signal with a cleavage that a three extracellular CUB P. G. J. Biol. PubMed Scopus Google with the of p80 to WGA, and a transmembrane with a cytoplasmic cytoplasmic tyrosine phosphorylation sites. This is with the tyrosine phosphorylation of p80. the of p80 in the identified that we a cDNA or the of the of p80. p80 a of Phosphorylation of the p80 cDNA was with the human on the and identified that to gene CUB protein 1 and W. P. PubMed Scopus Google was to the of p80. of p80 was in of p80 and LC of in gp140 confirmed that was of in and and gp140 in a for PubMed Scopus Google was to p80 and and to to p80 the on the at gene was identified on elevated in human and W. P. PubMed Scopus Google Scholar). protein was the gene encodes a putative transmembrane protein of that the of the by the p80 cDNA the p80 for in the p80 This established that p80 is residues 5 tyrosine of tyrosine residues phosphorylation for tyrosine kinases and In two Src and and of the gene a glycoprotein p80. This the that a or precursor of p80 that is by the Phosphorylation of p80 and gp140 to a trypsin-sensitive precursor to p80 and phosphorylation of p80 by signaling or keratinocyte or that protein kinases to adherent and HKs. of the on phosphorylation of p80 by with or of or on phosphorylation of p80. In suramin, a with multiple reported a and phosphorylation of an 80-kDa protein and phosphorylated 80-kDa protein by suramin with P-p80 by trypsin detachment as as 1 and as as on phosphorylation of p80. identity of the p80 and the 80-kDa protein is established and for to as p80. suramin of adherent HKs also phosphorylation of a 140-kDa gp140 that was in the or HKs and In phosphorylated gp140 as a phosphorylated This that trypsin digestion of adherent HKs p80 by of an extracellular HKs suspended with gp140 1 and in by readhesion for as In the of HKs with suramin to phosphorylation of gp140. In response to suramin, the HKs to In the of suramin, was low of P-p80 at by suramin and This that the in P-p80 protein In a of an of protein of gp140 trypsin HKs gp140 in that of gp140 Treatment of adherent HKs with for to trypsin digestion or of or the trypsin digestion on of phosphorylated p80 or gp140 by of cultured keratinocytes also tyrosine phosphorylation of p80 and gp140 and on of and epithelial This that is in also to phosphorylation of p80 and and of to the of suramin and phosphorylation of p80 and gp140. the used to cell is also an of suramin and also phosphorylation of a suramin of the two 1999; PubMed Scopus Google to the of This established that suramin or promotes phosphorylation of gp140 and p80 by with an extracellular or also that trypsin gp140 to p80. of and as a to p80 was and identified by LC to is a trypsin-sensitive precursor to p80 and the of HKs with suramin to phosphorylation of gp140. was a of the used for of of HKs was with and with and with and with and gp140 was with of the by LC was the protein identified in the gp140 serum in two of and in the two of the This identified gp140 as of the identified is in We conclude that cell gp140 is the protein by the gene and a trypsin-sensitive precursor to p80. of and of the of gp140 to transmembrane p80 p80 was the identified in p80 trypsin digestion of gp140 in HKs. cleavage at an of gp140 on the of in CUB and PTPs phosphorylation of gp140 by a tyrosine a PTP(s). that tyrosine phosphorylation of p80 and gp140 with of Src family kinases J. Biol. 1996; PubMed Scopus Google and J. Biol. 2000; PubMed Scopus Google phosphorylation of p80 and gp140 in adherent HKs and and also phosphorylation of p80 in HKs In phosphorylation of kinase inhibitors including and and and or on phosphorylation of gp140 or p80. for and at and for of p80 phosphorylation by with in and suggest that phosphorylation of gp140 and p80 in response to suramin equilibrium of phosphorylated gp140 also on PTPs that in or as inhibitors of and P-p80 the in phosphorylation of gp140 in response to vanadate was by with a is in adherent of resulting in low equilibrium of and a in phosphorylation of gp140 or p80 to membrane and of with is extracellular suramin increases phosphorylation of the cytoplasmic of reported to PTPs Y. J. Biol. PubMed Scopus Google in suramin vanadate to cytoplasmic PTPs to This is suramin is and phosphorylation of FAK, vanadate extracellular suramin an to two by in in the or of suramin and of in the of HKs In suramin of that vanadate of the in the J. Biol. PubMed Scopus Google and that suramin suramin of are of We conclude that suramin is a of PTPs in of HKs with suramin and promotes phosphorylation of We suggest that suramin with a cell a to phosphorylation of gp140 and p80. phosphorylation of gp140 and p80 via phosphorylation of including in 1 and This that suramin was We confirmed by with a polyclonal an Src phosphorylation phosphotyrosine in the with P-FAK, also with P-p80 and with suramin 1 and In phosphotyrosine in with P-p80 or of with and P-p80 was with a for tyrosine and the and cytoplasmic of gp140 5 tyrosine and are for phosphorylation by a for gp140 tyrosine was and of to P-p80 and and In gp140 and on of to or P-p80 5 and and and for gp140 tyrosine was for of to to In for gp140 on of to in adherent HKs This that gp140 is phosphorylated by and that with phosphorylated that gp140 is the phosphorylation is as for gp140 as is for a for of P-p80 and and gp140 and p80 that the trypsin and phosphorylation studies on for we a human gp140 cDNA with green fluorescent protein at the was in human epithelial and was as was with in of a and in the with and and and and with and and gp140 or p80 the gp140 cDNA was as a digestion and detachment of cell to to the This confirmed that gp140 is a trypsin-sensitive precursor to p80. trypsin digestion of the to the is cytoplasmic or and to extracellular of phosphorylation of by with that with gp140 with the and with the or This the of the for on the of protein that suramin protein suramin, the in was phosphorylated at at a that was the for gp140 in HKs. This that gp140 is phosphorylated in the of suramin or In we also gp140 in gp140 also a high phosphorylation with of or PTPs HKs. of the elevated phosphorylation in the is the that the cDNA encodes the membrane that we identified on tyrosine phosphorylation (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google Scholar). phosphorylation of gp140 and p80 in or by or to changes in trypsin digestion and suramin that the trypsin and phosphorylation studies on for and that gp140 and p80 are phosphorylated in the of and to the to the membrane in keratinocytes or we of HKs with a for and suramin and the HKs with or suramin, and and with that with gp140 phosphotyrosine suramin, was with in the focal of the adherent HKs In the focal in the focal with in the of suramin, membrane on and of the adherent HKs the focal and in focal gp140 the and membrane at was by of with with phosphorylation of mediated by We conclude that phosphorylation of at tyrosine in the membrane of HKs is in a of dynamic equilibrium mediated by and a low phosphorylation of gp140 suramin is Conversion of gp140 to p80 Phosphorylation of p80 gp140 we the of conversion of gp140 to p80 and the of the conversion on the phosphorylation of of gp140 p80 in response to suramin or changes in adhesion. we that the conversion of gp140 to p80 in wounds. Phosphorylated p80 is in and of HKs with or suramin 1 and In is in HKs with suramin or inhibitors of PTPs or In of the was P-p80 and of by of HKs converts gp140 to p80 and gp140 with and yielding p80 and HKs with a suramin to and P-p80 to suramin, and for the 1 the of suramin, was In was of the of of the adherent HKs with suramin the and that gp140 was in inhibitors of PTPs to suramin in phosphorylation of gp140 and to the suramin that the of was to a and of gp140 In with phosphorylation of p80 was and P-p80 was the of suramin This gp140 and p80 the relative abundance of P-p80 upon or in Based on we phosphorylation of gp140 and p80 was on response to used to phosphorylation of gp140 and p80. Phosphorylation of gp140 was at suramin with for p80 phosphorylated p80 a in and phosphorylation of p80 is to suramin the two that conversion of gp140 to p80 in the extracellular phosphorylation of the cytoplasmic Phosphorylation of gp140 p80 adhesion also phosphorylation of gp140 phosphorylation of p80. is by the that trypsin used to also converts gp140 to p80. we used the we that of HKs with to phosphorylation of suramin of the phosphorylation of gp140 In of HKs that gp140 to p80 phosphorylation of p80 and detachment phosphorylation of p80 gp140. we phosphorylation of detachment of converts to and the phosphorylated in the and the that was to trypsin was This the that the trypsin detachment dephosphorylated gp140 p80. This was as are the by trypsin digestion or of the with dephosphorylated with We conclude that phosphorylation of gp140 and p80 are altered by adhesion, are detachment dephosphorylates gp140 and phosphorylates p80. conversion of gp140 to p80 distinguishes phosphorylation of p80 phosphorylation of gp140. and phosphorylation of p80 is gp140. Conversion of gp140 to p80 by we that gp140 to p80 as a in wounds. Wounding of epidermis keratinocytes to in and serum that and and gp140 to p80. we a in serum that keratinocytes in gp140 to p80. of gp140 in HKs or in with was to gp140 to p80. that 1 on adherent HKs for was to gp140 and p80. This of is the of plasminogen in J. Biol. PubMed Google Scholar). a in to gp140 to p80 converts precursor laminin 5 to laminin 5 with on or adhesion in to trypsin that and trypsin phosphorylation of p80 relative to gp140 was or in epidermis is to gp140 to p80. was and with suramin to phosphorylation of gp140 and p80. with in laminin 5 the of the epidermis the epidermis with and P-p80 in the converts gp140 to p80. an in epidermis converts gp140 to p80, that gp140 in epithelial in In of and epithelial phosphorylation of p80 is by cell to the laminin dephosphorylates P-p80 and W. G. Carter, we P-p80 HKs and adherent HKs and a recombinant the are in a in and are as gp140 is a transmembrane glycoprotein and the trypsin-sensitive precursor to p80 and gp140 and p80 three extracellular CUB of gp140 is the of the gene that is in human and W. P. PubMed Scopus Google Scholar). in serum that in converts gp140 to p80 conversion increases phosphorylation of p80 relative to gp140 in response to extracellular adhesion or suramin and phosphorylation of gp140 on and tyrosine residues is mediated by Phosphorylation of gp140 is balanced by by an yielding low equilibrium phosphorylation of gp140 suramin, or adhesion phosphorylation of gp140 and p80 by the balance of and PTPs and We conclude that conversion of gp140 to p80 the phosphorylation balance mediated by and Conversion prolongs phosphorylation of p80 relative to gp140 in response to adhesion or We suggest that cleavage and adhesion transmembrane that phosphorylation of gp140 p80 in epithelial wounds. a CUB and a of the and p80 three CUB CUB residues in an extracellular an to P. G. J. Biol. PubMed Scopus Google Scholar, E. Biol. 1997; PubMed Scopus Google Scholar). CUB the three identified with the protein and protein 1 CUB are to in adhesion as the J. G. S. J. G. J. PubMed Scopus Google E. Biol. 1997; PubMed Scopus Google and J. Biol. PubMed Scopus Google and including and P. G. J. Biol. PubMed Scopus Google Scholar). is by the is elevated in human and the of a novel cell glycoprotein, was reported as the of the gene and a for PubMed Scopus Google Scholar). P-p80 was identified in a for phosphorylation in an wound model (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google Scholar). wound with is a Dermatol. PubMed Scopus Google Scholar). to phosphorylation or is altered in with adhesion M.C. Y. Carter W.G. J. Cell Biol. 1999; PubMed Scopus Google Scholar). gp140 to p80 of epidermis and P-p80 This that conversion of gp140 to p80 in via an a of we with adhesion in laminin for of the epidermis This the that conversion of gp140 to p80 is elevated in laminin 5 relative to Plasmin, a in converts gp140 to p80 and suggest that serum keratinocytes in and gp140 to p80. are to the of the trypsin and cleavage in gp140. Conversion of gp140 to p80 of the CUB with the and CUB domains, the and the cytoplasmic tyrosine phosphorylation sites. Sequencing of p80 identified of as the of the identified p80 trypsin the resulting p80 trypsin gp140 at residues or on the of for identified as J. Scopus Google Scholar). in gp140 that are for cleavage in trypsin and gp140 at sites. Phosphorylation of gp140 by and suramin or increases phosphorylation of p80 and gp140 by signaling an cell Cell detachment via trypsin phosphorylates p80, suramin phosphorylates gp140 and p80 at by of PTPs with vanadate also phosphorylation of gp140 and p80. of with the of suramin, or that the kinase is also for the in phosphorylation. This that is a dynamic balance of SFK, and low equilibrium phosphorylation of gp140 in adherent HKs and dynamic phosphorylation is by conversion of gp140 to p80 or cell detachment or suramin that increases phosphorylation of gp140 and p80. is a S. J. E. P. P. J. 2000; PubMed Scopus Google and heparin reported to tyrosine phosphorylation of and 140-kDa identified J. PubMed Scopus Google Scholar). including J. J. Biol. PubMed Google and of keratinocytes J. Cell Google in S. J. PubMed Scopus Google J. PubMed Scopus Google and cell on and laminin Y. Cell PubMed Scopus Google Scholar). of suramin on cell are to on signaling J. Cell Google Scholar). suramin also PTPs J. PubMed Scopus Google J. J. Biol. PubMed Google and urokinase plasminogen to E. G. PubMed Scopus Google and activates protein kinase W. PubMed Scopus Google Scholar). suramin promotes phosphorylation of gp140 and p80 at that are to PTPs in cell J. PubMed Scopus Google including phosphorylation of of Phosphorylation of gp140 and p80 and in and the of to p80. trypsin increases phosphorylation at and cytoplasmic tyrosine residues of p80, relative to gp140 trypsin conversion of gp140 to p80 cell detachment to to the relative in phosphorylation of p80. trypsin conversion with cell prolongs phosphorylation of p80 relative to conversion of gp140 to p80 the prolongs phosphorylation of p80. This that prolongs phosphorylation. phosphorylation of p80 to the in phosphorylation of p80 in in and detachment conversion increases phosphorylation of p80 in We that detachment and increases in of HKs with as and W. G. Carter, This of for in phosphorylation of gp140 and p80. gp140 and p80 are phosphorylated transmembrane of epithelial in suramin, adhesion, or and W. G. Carter, to PTPs to phosphorylation of gp140 and p80. is conversion of gp140 to p80 the of the extracellular on phosphorylation p80 and gp140 Conversion of gp140 to p80 of p80 with or or of p80 relative to gp140 to the phosphorylation. (4Xia Y. Gil S.G. Carter W.G. J. Cell Biol. 1996; 132: 727-740Crossref PubMed Scopus (116) Google and G. and W. G. Carter, that adhesion, cell or is for the of p80 upon In the of adhesion to laminin 5 via α6β4 or is to p80. This that α6β4 or laminin 5 in the extracellular to and PTPs in the and transmembrane adhesion to phosphorylation of gp140 and adhesion SFK, FAK, and to E. S. S. J. Cell Biol. PubMed Scopus Google Scholar, Y. J. Biol. PubMed Scopus Google Scholar). E. S. S. J. Cell Biol. PubMed Scopus Google Scholar, Y. J. Biol. PubMed Scopus Google Scholar, J. Biol. PubMed Scopus Google and Ryan S. 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PubMed Scopus Google Scholar). the to gp140 to p80. of to laminin 5 or to phosphorylation of gp140 and p80 We that conversion of gp140 to p80 in keratinocytes a transmembrane signal in that is to adhesion to laminin studies to the for gp140 and p80 in and the of adhesion, and phosphorylation in that We for of the and for