The insulin-like growth factor II/mannose-6-phosphate receptor

Alexandrides T, Moses AC and Smith RJ (1989) Developmental expression of receptors for insulin, insulin-like growth factor I (IGF-I), and IGF-II in rat skeletal muscle. Endocrinology 124: 1064–1076. Appell KC, Simpson IA and Cushman SW (1988) Characterization of the stimulatory action of insulin on insulin-like growth factor II binding to rat adipose cells. J. Biol. Chem. 263: 10824–10829. August GP, Nissley SP, Kasuga M, Lee L, Greenstein L and Recher MM (1983) Purification of an insulin-like growth factor II receptor from rat chondrosarcoma cells. J. Biol. Chem. 258: 9033–9036. Braulke T, Causin C, Waheed A, Junghans U, Hasilik A, Maly P, Humbel RE and von Figura K (1988) Mannose 6-phosphate/insulin-like growth factor II receptor: distinct binding sites for mannose 6-phosphate and insulin-like growth factor II. Biochem. Biophys. Res. Commun. 150: 1287–1293. Braulke T, Gartung C, Hasilik A and von Figura K (1987) Is movement of mannose 6-phosphate-specific receptor triggered by binding of lysosomal enzymes? J. Cell Biol. 104: 1735–1742. Braulke T, Tippmer S, Neher E and von Figura K (1989) Regulation of the mannose 6-phosphate/IGF II receptor expression at the cell surface by mannose 6-phosphate, insulin like growth factors and epidermal growth factor. EMBO J. 8: 681–686. Brown WJ and Farquhar MG (1984) The mannose-6-phosphate receptor for lysosomal enzymes is concentrated in cis Golgi cisternae. Cell 36: 295–307. Brown WJ and Farquhar MG (1987) The distribution of 215-kilodalton mannose 6-phosphate receptors within cis (heavy) and trans (light) Golgi subfractions varies in different cell types. Proc. Natl. Acad. Sci., USA 84: 9001–9005. Brown WJ, Goodhouse J and Farquhar MG (1986) Mannose-6-phosphate receptors for lysosomal enzymes cycle between the Golgi complex and endosomes. J. Cell Biol. 103: 1235–1247. Canfield WM and Kornfeld S (1989) The chicken liver cation-independent mannose 6-phosphate receptor lacks the high affinity binding site for insulin-like growth factor II. J. Biol. Chem. 264: 7100–7103. Causin C, Waheed A, Braulke T, Junghans U, Maly P, Humbel RE and von Figura K (1988) Mannose 6-phosphate/insulin-like growth factor II-binding proteins in human serum and urine. Biochem. J. 252: 795–799. Clairmont KB and Czech MP (1989) Chicken and frog mannose-6-phosphate receptors fail to bind insulin-like growth factor II. 71st Annual Meeting of the Endocrine Society, Seattle, WA, Abstract No. 100. Corvera S and Czech MP (1985) Mechanism of insulin action on membrane protein recycling: A selective decrease in the phosphorylation state of insulin-like growth factor II receptors in the cell surface membrane. Proc. Natl. Acad. Sci. USA 82: 7314–7318. Corvera S, Folander K, Clairmont KB and Czech MP (1988a) A highly phosphorylated subpopulation of insulin-like growth factor II/mannose 6-phosphate receptors is concentrated in a clathrin-enriched plasma membrane fraction. Proc. Natl. Acad. Sci. USA 85: 7567–7571. Corvera S, Roach PJ, DePaoli-Roach AA and Czech MP (1988b) Insulin action inhibits insulin-like growth factor-II (IGF-II) receptor phosphorylation in H-35 hepatoma cells. J. Biol. Chem. 263: 3116–3122. Corvera S, Whitehead RE, Mottola C and Czech MP (1986) The insulin-like growth factor II receptor is phosphorylated by a tyrosine kinase in adipocyte plasma membranes. J. Biol. Chem. 261: 7675–7679. Creek KE and Sly WS (1983) Biosynthesis and turnover of the phosphomannosyl receptor in human fibroblasts. Biochem. J. 214: 353–360. Czech MP (1982) Structural and functional homologies in the receptors for insulin and the insulin-like growth factors. Cell 31: 8–10. Dahms NM, Lobel P, Breitmeyer J, Chirgwin JM and Kornfeld S (1987) 46 kd Mannose 6-phosphate receptor: Cloning, expression, and homology to the 215 kd mannose 6-phosphate receptor. Cell 50: 181–192. Daughaday WH and Rotwein P (1989) Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocrine Rev. 10: 68–91. Daughaday WH, Kapadia M, Yanow CE, Fabrick K and Mariz IK (1985) Insulin-like growth factors I and II of nonmammalian sera. Gen. Comp. Endocrinol. 59: 316–325. Daughaday WH, Mariz IK and Trivedi B (1981) A preferential binding site for insulin-like growth factor II in human and rat placental membranes. J. Clin. Endo. Metab. 53: 282–288. Dawe SR, Francis GL, McNamara PJ, Wallace JC and Ballard FJ (1988) Purification, partial sequences and properties of chicken insulin-like growth factors. J. Endocrinol. 117: 173–181. Distler J, Heiber V, Sahagian G, Schmickel R, and Jourdian GW (1979) Identification of mannose 6-phosphate in glycoproteins that inhibit the assimilation of β-galactosidase by fibroblasts. Proc. Natl. Acad. Sci. USA 76: 4235–4239. Duncan JR and Kornfeld S (1988) Intracellular movement of two mannose-6-phosphate receptors: return to the Golgi apparatus. J. Cell Biol. 106: 617–628. Fischer HD, Creek KE and Sly WS (1982) Binding of phosphorylated oligosaccharides to immobilized phosphomannosyl receptors. J. Biol. Chem. 257: 9938–9943. Gabel CA, Goldberg DE and Kornfeld S (1983) Identification and characterization of cells deficient in the mannose 6-phosphate receptor: evidence for an alternate pathway for lysosomal enzyme targeting. Proc. Natl. Acad. Sci. USA 80: 775–779. Gelato MC, Kiess W, Lee L, Malozowski S, Rechler MM and Nissley P (1988) The insulin-like growth factor II/ mannose-6-phosphate receptor is present in monkey serum. J. Clin. Endocrinol. Metab. 67: 669–675. Gelato MC, Rutherford C, Stark RI and Daniel SS (1989) The insulin-like growth factor II/mannose-6-phosphate receptor is present in fetal and maternal sheep serum. Endocrinology 124: 2935–2943. Geuze HJ, Slot JW, Strous GJAM, Hasilik A and von Figura K (1984a) Ultrastructural localization of the mannose 6-phosphate receptor in rat liver. J. Cell Biol. 98: 2047–2054. Geuze HJ, Slot JW, Strous GJAM, Hasilik A and von Figura K (1985) Possible pathways for lysosomal enzyme delivery. J. Cell Biol. 101: 2253–2262. Geuze HJ, Slot JW, Strous GJAM, Peppard J, von Figura K, Hasilik A and Schwartz AL (1984b) Intracellular receptor sorting during endocytosis: comparative immunoelectron microscopy of multiple receptors in rat liver. Cell 37: 195–204. Gieselmann V, Pohlmann R, Hasilik A and von Figura K (1983) Biosynthesis and transport of cathepsin D in cultured human fibroblasts. J. Cell Biol. 97: 1–5. Glickman JN, Conibear E and Pearse BMF (1989) Specificity of binding of clathrin adaptors to signals on the mannose-6-phosphate/insulin-like growth factor II receptor. EMBO J. 8: 1041–1047. Goda Y and Pfeffer SR (1988) Selective recycling of the mannose 6 phosphate/IGF-II receptor to the trans Golgi network in vitro. Cell 55: 309–320. Goldberg DE, Gabel CA and Kornfeld S (1983) Studies of the biosynthesis of the mannose 6-phosphate receptor in receptor-positive and-deficient cell lines. J. Cell Biol. 97: 1700–1706. Hari J, Pierce SB, Morgan DO, Sara V, Smith MC and Roth RA (1987) The receptor for insulin-like growth factor II mediates an insulin-like response. EMBO J. 6: 3367–3371. Hasilik A and Neufeld E (1980) Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. J. Biol. Chem. 255: 4946–4950. Herzog V, Neumuller W and Holzmann B (1987) Thyroglobulin, the major and obligatory exportable protein of thryroid follicle cells, carries the lysosomal recognition marker mannose-6-phosphate. EMBO J. 6: 555–560. Hickman S, Shapiro LJ and Neufeld EF (1974) A recognition marker required for uptake of a lysosomal enzyme by cultured fibroblasts. Biochem. Biophys. Res. Commun. 57: 55–61. Hoflack B and Kornfeld S (1985b) Purification and characterization of a cation-dependent mannose 6-phosphate receptor from murine P388D1 macrophages and bovine liver. J. Biol. Chem. 260: 12008–12014. Hoflack B and Kornfeld S (1985a) Lysosomal enzyme binding to mouse P388D1 macrophage membranes lacking the 215-kDa mannose 6-phosphate receptor: evidence for the existence of a second mannose 6-phosphate receptor. Proc. Natl. Acad. Sci. USA 82: 4428–4432. Hoflack B, Fujimoto K and Kornfeld S (1987) The interaction of phosphorylated oligoscccharides and lysosomal enzymes with bovine liver cation-dependent mannose 6-phosphate receptor. J. Biol. Chem. 262: 123–129. Hynes RO (1981) Fibronectin and its relation to cellular structure and behavior. In: ED Hay (ed) Cell Biology of the Extracellular Matrix (pp. 295–334) Plenum, New York. Jacobs S, Hazum E and Cuatrecasas P (1980) The subunit structure of rat liver insulin receptor. J. Biol. Chem. 255: 6937–6940. Jacobs S (1985) Immunochemical characterization of receptors for insulin and insulin-like growth factor I. In: MP Czech (ed) Molecular Basis of Insulin Action (pp. 31–44) Plenum Press, New York. Jin M, Sahagian GG and Snider MD (1989) Transport of surface mannose 6-phosphate receptor to the Golgi complex in cultured human cells. J. Biol. Chem. 264: 7675–7680. Kaplan A, Achord DT and Sly WS (1977) Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts. Proc. Natl. Acad. Sci. USA 74: 2026–2030. Kaplan A, Fischer D and Sly WS (1978) Correlation of structural features of phosphomannans with their ability to inhibit pinocytosis of human \-glucuronidase by human fibroblasts. J. Biol. Chem. 253: 647–650. Kasuga M, Van Obberghen E, Nissley SP and Rechler MM (1981) Demonstration of two subtypes of insulin-like growth factor receptors by affinity cross-linking. J. Biol. Chem. 256: 5305–5308. Kasuga M, Van Obberghen E, Nissley SP and Rechler MM (1982) Structure of the insulin-like growth factor receptor in chicken embryo fibroblasts. Proc. Natl. Acad. Sci. USA 79: 1864–1868. Kiess W, Blickenstaff GD, Sklar MM, Thomas CL, Nissley SP and Sahagian GG (1988) Biochemical evidence that the type II insulin-like growth factor receptor is identical to the cation-independent mannose 6-phosphate receptor. J. Biol. Chem. 263: 9339–9344. Kiess W, Greenstein LA, White RM, Lee L, Rechler MM and Nissley SP (1987) Type II insulin-like growth factor receptor is present in rat serum. Proc. Natl. Acad. Sci. USA 84: 7720–7724. Kiess W, Thomas CL, Greenstein LA, Lee L, Sklar MM, Rechler MM, Sahagian GG and Nissley SP (1989) Insulin-like growth factor-II (IGF-II) inhibits both the cellular uptake of β-galactosidase and the binding of β-galactosidase to purified IGF-II/mannose 6-phosphate receptor. J. Biol. Chem. 264: 4710–4714. King GL, Rechler MM and Kahn CR (1982) Interactions between the receptors for insulin and the insulin-like growth factors on adipocytes. J. Biol. Chem. 257: 10001–10006. Kojima I, Nishimoto I, Iiri T, Ogata E and Rosenfeld R (1988) Evidence that type II insulin-like growth factor receptor is coupled to calcium gating system. Biochem. Biophys. Res. Commun. 154: 9–19. Kornfeld S (1987) Trafficking of lysosomal enzymes. FASEB J. 1: 462–468. Kovacina KS, Steele-Perkins G, Purchio AF, Lioubin M, Miyazumo K, Henrik-Heldin C and Roth RA (1989) Interactions of recombinant and platelet transforming growth factor-β1 precursor with the insulin-like growth factor II/mannose 6-phosphate receptor. Biochem. Biophys. Res. Commun. 160: 393–403. Kyle JW, Nolan CM, Oshima A and Sly WS (1988) Expression of human cation-independent mannose 6-phosphate receptor cDNA in receptor-negative mouse P388D1 cells following gene transfer. J. Biol. Chem. 263: 16230–16235. Laiho M and Keski-Oja J (1989) Growth factors in the regulation of pericellular proteolysis: A review. Cancer Res. 49: 2533–2553. Lee S-J and Nathans D (1988) Proliferin secreted by cultured cells binds to mannose 6-phosphate receptors. J. Biol. Chem. 263: 3521–3527. Liotta LA (1986) Tumor invasion and metastases-role of the extracellular matrix. Cancer Res. 46: 1–7. Lobel P, Dahms NM and Kornfeld S (1988) Cloning and sequence analysis of the cation-independent mannose 6-phosphate receptor. J. Biol. Chem. 263: 2563–2570. Lobel P, Dahms NM, Greitmeyer J, Chirgwin JM and Kornfeld S (1987) Cloning of the bovine 215-kDa cation-independent mannose 6-phosphate receptor. Proc. Natl. Acad. Sci. USA 84: 2233–2237. Lobel P, Fujimoto K, Ye RD, Griffiths G and Kornfeld S (1989) Mutations in the cytoplasmic domain of the 275 kd mannose 6-phosphate receptor differentially alter lysosomal enzyme sorting and endocytosis. Cell 57: 787–796. MacDonald RG and Czech MP (1985) Biosynthesis and processing of the type II insulin-like growth factor receptor in H-35 hepatoma cells. J. Biol. Chem. 260; 11357–11365. MacDonald RG, Pfeffer SR, Coussens L, Tepper MA, Brocklebank CM, Mole JE, Anderson JK, Chen E, Czech MP and Ullrich A (1988) A single receptor binds both insulin-like growth factor II and mannose-6-phosphate. Science 239: 1134–1137. MacDonald RG, Tepper MA, Clairmont KB, Perregaux SB and Czech MP (1989) Serum form of the rat insulin-like growth factor II/mannose 6-phosphate receptor is truncated in the carboxyl-terminal domain. J. Biol. Chem. 264: 3256–3261. Massague J and Czech MP (1982) The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J. Biol. Chem. 257:5038–5045. Mellas J, Gavin JRIII and Hammerman MR (1986) Multiplication-stimulating activity-induced alkalinization of canine renal proximal tubular cells. J. Biol. Chem. 261: 14437–14442. Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA and Rutter WJ (1987) Insulin-like growth factor II receptor as a multifunctional binding protein. Nature 329: 301–307. Mottola C and Czech MP (1984) The type II insulin-like growth factor receptor does not mediate increased DNA synthesis in H-35 hepatoma cells. J. Biol. Chem. 259: 12705–12713. Neufeld EF, Lim TW and Shapiro LJ (1975) Inherited disorders of lysosomal metabolism. Annu. Rev. Biochem. 44: 357–376. Neufeld EF, Sando GN, Garvin AJ and Rome LH (1977) The transport of lysosomal enzymes. J. Supramol. Struct. 6: 95–101. Nishimoto I, Hata Y, Ogata E and Kojima I (1987) Insulin-like growth factor II stimulates calcium influex in competent BALB/c 3T3 cells primed with epidermal growth factor. J. Biol. Chem. 262: 12120–12126. Nissley SP, Rechler MM, Moses AC, Short PA and Podskalny JM (1977) Proinsulin binds to a growth peptide receptor and stimulates DNA synthesis in chick embryo fibroblasts. Endocrinology 101: 708–716. Oka Y and Czech MP (1986) The type II insulin-like growth factor receptor is internalized and recycles in the absence of ligand. J. Biol. Chem. 261: 9090–9093. Oka Y, Kasuga M, Kanazawa Y and Takaka F (1987) Insulin induces chloroquine-sensitive recycling of insulin-like growth factor II receptors but not of glucose transporters in rat adipocytes. J. Biol. Chem. 262: 17480–17486. Oka Y, Mottola C, Oppenheimer CL and Czech MP (1984) Insulin activates the appearance of insulin-like growth factor II receptors on the adipocyte cell surface. Proc. Natl. Acad. Sci. USA 81: 4028–4032. Oka Y, Rozek LM and Czech MP (1985) Direct demonstration of rapid insulin-like growth factor II receptor internalization and recycling in rat adipocytes. J. Biol. Chem. 260: 9435–9442. Oppenheimer CL and Czech MP (1983) Purification of the type II insulin-like growth factor receptor from rat placenta. J. Biol. Chem. 258: 8539–8542. Oppenheimer CL, Pessin JE, Massague J, Gitomer W and Czech MP (1983) Insulin action rapidly modulates the apparent affinity of the insulin-like growth factor II receptor. J. Biol. Chem. 258: 4824–4830. Oshima A, Nolan CM, Kyle JW, Grubb JH and Sly WS (1988) The human cation-independent mannose 6-phosphate receptor. J. Biol. Chem. 263: 2553–2562. Pearse BMF (1988) Receptors compete for adaptors found in plasma membrane coated pits. EMBO J. 7: 3331–3336. Perdue JF, Chan JK, Thibault C, Radaj P, Mills B and Daughaday WH (1983) The biochemical characterization of detergent-solubilized insulin-like growth factor II receptors from rat placenta. J. Biol. Chem. 258: 7800–7811. Pfeffer SR (1987) The endosomal concentration of a mannose 6-phosphate receptor is unchanged in the absence of ligand-synthesis. J. Cell Biol. 105: 229–234. Pilch PF and Czech MP (1979) Interaction of cross-linking agents with the insulin effector system of isolated fat cells. J. Biol. Chem. 254: 3375–3381. Pilch PF and Czech MP (1980) The subunit structure of the high affinity insulin receptor. J. Biol. Chem. 255: 1722–1731. Pohlmann R, Nagel G, Schmidt B, Stein M, Lorkowski G, Krentler C, Cully J, Meyer HE, Grzechik K-H, Mersann G, Hasilik A and von Figura K (1987) Cloning of a cDNA encoding the human cation-dependent mannose 6-phosphate-specific receptor. Proc. Natl. Acad. Sci. USA 84: 5575–5579. Polychronakos C, Guyda HJ and Posner BI (1988) Mannose 6-phosphate increases the affinity of its cation-independent receptor for insulin-like growth factor II by displacing inhibitory endogenous ligands. Biochem. Biophys. Res. Commun. 157: 632–638. Purchio AF, Cooper JA, Brunner AM, Lioubin MN, Gentry LE, Kovacina KS, Roth RA and Marquardt H (1988) Identification of mannose 6-phosphate in two asparagine-linked sugar chains of recombinant transforming growth factor-β1 precursor. J. Biol. Chem. 263: 14211–14215. Rechler MM and Nissley SP (1985) The nature and regulation of the receptors for insulin-like growth factors. Annu. Rev. Physiol. 47:425–442. Rechler MM, Zapf J, Nissley SP, Froesch ER, Moses AC, Podskalny JM, Schilling EE and Humbel RE (1980) Interactions of insulin-like growth factors I and II and multiplication-stimulating activity with receptors and serum carrier proteins. Endocrinology 107: 1451–1459. Rinderknecht E and Humbel RE (1978a) The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J. Biol Chem. 253: 2769–2776. Rinderknecht E and Humbel RE (1978b) Primary structure of human insulin-like growth factor II. FEBS Lett. 89: 283–286. Rogers SA and Hammerman MR (1988) Insulin-like growth factor II stimulates production of inositol trisphosphate in proximal tubular basolateral membranes from canine kidney. Proc. Natl. Acad. Sci. USA 85: 4037–4041. Rogers SA and Hammerman MR (1989) Mannose 6-phosphate potentiates insulin-like growth factor II-stimulated inositol trisphosphate production in proximal tubular basolateral membranes. J. Biol. Chem. 264: 4273–4276. Romanus JA, Yang YW-H, Adams SO, Sofair AN, Tseng LY-H, Nissley SP and Rechler MM (1988) Synthesis of insulin-like growth factor-II (IGF-II) in fetal rat tissues: translation of IGF-II ribonucleic acid and processing of pre-pro-IGF-II. Endocrinology 122: 709–716. Rome LH, Weissmann B and Neufeld EF (1979) Direct demonstration of binding of a lysosomal enzyme, α-L-iduronidase, to receptors on cultured fibroblasts. Proc. Natl. Acad. Sci. USA 76: 2331–2334. Rosen OM (1987) After insulin binds. Science 237: 1452–1458. Roth J, Taatjes DJ, Lucocq JM, Weinstein J and Paulson JC (1985) Demonstration of an extensive trans-tubular network continuous with the Golgi apparatus stack that may function in glycosylation. Cell 43: 287–295. Roth RA (1985) Structure of the receptor for insulin-like growth factor II: The puzzle amplified. Science 239: 1269–1271. Roth RA, Stover C, Hari J, Morgan DO, Smith MC, Sara V and Fried VA (1987) Interactions of the receptor for insulin-like growth factor II with mannose-6-phosphate and antibodies to the mannose-6-phosphate receptor. Biochem.. Biophys. Res. Commun. 149: 600–606. Sahagian GG (1984) The mannose 6-phosphate receptor: function, biosynthesis and translocation. Biol. Cell 51: 207–214. Sahagian GG and Neufeld EF (1983) Biosynthesis and turnover of the mannose 6-phosphate receptor in cultured chinese hamster ovary cells. J. Biol. Chem. 258: 7121–7128. Sahagian GG, Distler J and Jourdian GW (1981) Characterization of a membrane-associated receptor from bovine liver that binds phosphomannosyl residues of bovine testicular β-galactosidase. Proc. Natl. Acad. Sci. USA 78: 4289–4293. Schoenle E, Zapf J and Froesch ER (1977) Effects of insulin and NSILA on adipocytes of normal and diabetic rats: receptor binding, glucose transport and glucose metabolism. Diabetologia 13: 243–249. Stein M, Meyer HE, Hasilik A and von Figura K (1987) 46-kDa Mannose 6-phosphate-specific receptor: purification, subunit composition, chemical modification. Biol. Chem. Hoppe-Seyler 368: 927–936. Tally M, Li CH and Hall K (1987) IGF-2 Stimulated growth mediated by the somatomedin type 2 receptor. Biochem. Biophys. Res. Commun. 148: 811–816. Tanner LI and Lienhard GE (1989) Localization of transferrin receptors and insulin-like growth factor II receptors in vesicles from 3T3-L1 adipocytes that contain intracellular glucose transporters. J. Cell. Biol. 108: 1537–1545. Thibault C, Chan JK, Perdue JF and Daughaday WH (1984) Insulin-like growth factor II receptors. J. Biol. Chem. 259: 3361–3367. Todderud G and Carpenter G (1988) Presence of mannose phosphate on the epidermal growth factor receptor in A-431 cells. J. Biol. Chem. 263: 17893–17896. Tong PY, and Kornfeld S (1989) Ligand interactions of the cation-dependent mannose 6-phosphate receptor. J. Biol. Chem. 264: 7970–7975. Tong PY, Gregory W and Kornfeld S (1989) Ligand interactions of the cation-independent mannose 6-phosphate receptor. J. Biol. Chem. 264: 7962–7969. Tong PY, Tollefsen SE and Kornfeld S (1988) The cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II. J. Biol. Chem. 263: 2585–2588. Varki A and Kornfeld S (1983) The spectrum of anionic oligosaccharides released by endo-ß-N-acetylglucosaminidase H from glycoproteins. J. Biol. Chem. 258: 2808–2818. von Figura K and Hasilik A (1986) Lysosomal enzymes and their receptors. Annu. Rev. Biochem. 55: 167–193. von Figura K and Weber E (1978) An alternative hypothesis of cellular transport of lysosomal enzymes in fibroblasts. Biochem. J. 176: 943–950. von Figura K, Gieselmann V and Hasilik A (1984) Antibody to mannose 6-phosphate specific receptor induces receptor deficiency in human fibroblasts. EMBO J. 3: 1281–1286. von Figura K, Gieselmann V, and Hasilik A (1985) Mannose 6-phosphate-specific receptor is a transmembrane protein with a C-terminal extension oriented towards the cytosol. Biochem. J. 225: 543–547. Waheed A, Braulke T, Junghans U and von Figura K (1988) Mannose 6-phosphate/insulin like growth factor II receptor: the two types of ligands bind simultaneously to one receptor at different sites. Biochem. Biophys. Res. Commun. 152: 1248–1254. Wardzala LJ, Simpson IA, Rechler MM and Cushman SW (1984) Potential mechanism of the stimulatory action of insulin on insulin-like growth factor II binding to the isolated rat adipose cell. J. Biol. Chem. 259: 8378–8383. Westcott KR, Searles RP and Rome LH (1987) Evidence for ligand- and pH-dependent conformational changes in liposome-associated mannose 6-phosphate receptor. J. Biol. Chem. 262: 6101–6107. Willingham MC, Pastan IH and Sahagian GG (1983) Ultrastructural immunocytochemical localization of the phosphomannosyl receptor in Chinese hamster ovary (CHO) cells. J. Histochem. Cytochem. 31: 1–11. Yarden Y and Ullrich A (1988) Growth factor receptor tyrosine kinases. Annu. Rev. Biochem. 57: 443–478.