c3e950b46cabdba9f9a79bf02d15e23f pmc_34944082.pdf f43acc3b680368997f64c8f1680ef55fac316bda pmc_34944082.pdf 3c36099a321f44546a5896f20bc26b45183c9e2cded082e37ff8c20b5a505528 pmc_34944082.pdf Title: Pregnancy-Associated Plasma Protein (PAPP)-A2 in Physiology and Disease Subject: The growth hormone (GH)/insulin-like growth factor (IGF) axis plays fundamental roles during development, maturation, and aging. Members of this axis, composed of various ligands, receptors, and binding proteins, are regulated in a tissue- and time-specific manner that requires precise control that is not completely understood. Some of the most recent advances in understanding the implications of this axis in human growth are derived from the identifications of new mutations in the gene encoding the pregnancy-associated plasma protein PAPP-A2 protease that liberates IGFs from their carrier proteins in a selective manner to allow binding to the IGF receptor 1. The identification of three nonrelated families with mutations in the PAPP-A2 gene has shed light on how this protease affects human physiology. This review summarizes our understanding of the implications of PAPP-A2 in growth physiology, obtained from studies in genetically modified animal models and the PAPP-A2 deficient patients known to date. Keywords: growth hormone axis; IGF1; IGF2; IGFBPs; PAPP-A; PAPP-A2; STC1; STC2 Author: Vicente Barrios, Julie A. Chowen, Álvaro Martín-Rivada, Santiago Guerra-Cantera, Jesús Pozo, Shoshana Yakar, Ron G. Rosenfeld, Luis A. Pérez-Jurado, Juan Suárez and Jesús Argente Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Dec 20 15:12:12 2021 CET ModDate: Mon Dec 20 15:17:40 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2076656 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FJDQIS+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 YWQWLZ+VnURWPalladioL Type 1 Custom yes yes no 15 0 SHMLEW+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 QFAOMJ+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 EIREHE+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 MFFMGM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 81 0 MFFMGO+PalatinoLinotype TrueType WinAnsi yes yes no 84 0 MFFMHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 87 0 MFFMGM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 100 0 MFFMGO+PalatinoLinotype TrueType WinAnsi yes yes no 103 0 MFFMHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 106 0 MFGABM+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 109 0 GOCQIR+EURM10 Type 1 Builtin yes yes no 116 0 ZNCWCJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 123 0 MFFMGM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 133 0 MFFMGO+PalatinoLinotype TrueType WinAnsi yes yes no 136 0 MFFMHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 139 0 VFNYCD+CMSY10 Type 1 Builtin yes yes no 146 0 MFFMGM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 156 0 MFFMGO+PalatinoLinotype TrueType WinAnsi yes yes no 159 0 MFFMHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 162 0 MFFMGM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 185 0 MFFMGO+PalatinoLinotype TrueType WinAnsi yes yes no 188 0 MFFMHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 191 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-22 02:27:20 CET RepresentationInformation: pmc_34944082.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-01-10 07:58:41 CET Size: 2076656 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 554 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Mutations in the Human PAPP-A2 Gene Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Clinical Phenotype Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Auxology in PAPP-A2 Deficient Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Bone and Teeth Abnormalities Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Glucose Metabolism Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: PAPP-A2 Mouse Models: What Are We Learning? 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Chowen, Álvaro Martín-Rivada, Santiago Guerra-Cantera, Jesús Pozo, Shoshana Yakar, Ron G. Rosenfeld, Luis A. Pérez-Jurado, Juan Suárez and Jesús Argente Subject: The growth hormone (GH)/insulin-like growth factor (IGF) axis plays fundamental roles during development, maturation, and aging. Members of this axis, composed of various ligands, receptors, and binding proteins, are regulated in a tissue- and time-specific manner that requires precise control that is not completely understood. Some of the most recent advances in understanding the implications of this axis in human growth are derived from the identifications of new mutations in the gene encoding the pregnancy-associated plasma protein PAPP-A2 protease that liberates IGFs from their carrier proteins in a selective manner to allow binding to the IGF receptor 1. The identification of three nonrelated families with mutations in the PAPP-A2 gene has shed light on how this protease affects human physiology. This review summarizes our understanding of the implications of PAPP-A2 in growth physiology, obtained from studies in genetically modified animal models and the PAPP-A2 deficient patients known to date. 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Subtype: Link Rect: 478, 560, 515, 571 Annotation: Subtype: Link Rect: 102, 526, 139, 536 Annotation: Subtype: Link Rect: 245, 491, 283, 502 Annotation: Subtype: Link Rect: 289, 491, 325, 502 Annotation: Subtype: Link Rect: 297, 456, 335, 467 Annotation: Subtype: Link Rect: 433, 445, 471, 456 Annotation: Subtype: Link Rect: 183, 423, 221, 433 Annotation: Subtype: Link Rect: 227, 423, 263, 433 Annotation: Subtype: Link Rect: 86, 400, 124, 410 Annotation: Subtype: Link Rect: 130, 400, 166, 410 Annotation: Subtype: Link Rect: 295, 364, 333, 375 Annotation: Subtype: Link Rect: 520, 341, 557, 352 Annotation: Subtype: Link Rect: 104, 296, 141, 306 Annotation: Subtype: Link Rect: 331, 261, 369, 272 Annotation: Subtype: Link Rect: 116, 227, 154, 237 Annotation: Subtype: Link Rect: 216, 204, 253, 214 Annotation: Subtype: Link Rect: 259, 204, 295, 214 Annotation: Subtype: Link Rect: 319, 180, 357, 191 Annotation: Subtype: Link Rect: 349, 157, 386, 168 Annotation: Subtype: Link Rect: 314, 134, 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532, 479 Annotation: Subtype: Link Rect: 521, 456, 557, 467 Annotation: Subtype: Link Rect: 86, 434, 123, 444 Annotation: Subtype: Link Rect: 264, 411, 302, 421 Annotation: Subtype: Link Rect: 308, 411, 344, 421 Annotation: Subtype: Link Rect: 209, 388, 246, 398 Annotation: Subtype: Link Rect: 180, 364, 218, 375 Annotation: Subtype: Link Rect: 95, 331, 133, 341 Annotation: Subtype: Link Rect: 95, 285, 133, 295 Annotation: Subtype: Link Rect: 86, 250, 124, 260 Annotation: Subtype: Link Rect: 130, 250, 166, 260 Annotation: Subtype: Link Rect: 391, 226, 428, 237 Annotation: Subtype: Link Rect: 104, 192, 142, 203 Annotation: Subtype: Link Rect: 515, 169, 553, 180 Annotation: Subtype: Link Rect: 303, 134, 341, 145 Annotation: Subtype: Link Rect: 347, 134, 383, 145 Annotation: Subtype: Link Rect: 452, 111, 490, 122 Annotation: Subtype: Link Rect: 496, 111, 532, 122 Annotation: Subtype: Link Rect: 395, 77, 433, 88 Annotation: Subtype: Link Rect: 439, 77, 475, 88 Page: Sequence: 22 Annotations: Annotation: Subtype: Link Rect: 204, 721, 242, 732 Annotation: Subtype: Link Rect: 248, 721, 284, 732 Annotation: Subtype: Link Rect: 365, 698, 403, 709 Annotation: Subtype: Link Rect: 409, 698, 445, 709 Checksum: 4099a205 Type: CRC32 Checksum: c3e950b46cabdba9f9a79bf02d15e23f Type: MD5 Checksum: f43acc3b680368997f64c8f1680ef55fac316bda Type: SHA-1