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Insulin-like growth factor 2 receptor



Insulin-like growth factor 2 receptor
PDB rendering based on 1e6f.
Available structures: 1e6f, 1gp0, 1gp3, 1gqb, 2cnj
Identifiers
Symbol(s) IGF2R; CD222; CIMPR; M6P-R; MPRI
External IDs OMIM: 147280 MGI: 96435 Homologene: 676
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 3482 16004
Ensembl ENSG00000197081 ENSMUSG00000023830
Uniprot P11717 Q7TMR1
Refseq NM_000876 (mRNA)
NP_000867 (protein) 		NM_010515 (mRNA)
NP_034645 (protein)
Location Chr 6: 160.31 - 160.45 Mb Chr 17: 12.53 - 12.61 Mb
Pubmed search [1] [2]

In biochemistry and cell biology, the insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR), is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.

Contents

Structure

The structure of the IGF2R is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-terminus on the cytoplasmic side of lipid membranes) with a large extracellular/lumenal domain and a relatively short cytoplasmic tail (Ghosh, Dahms & Kornfeld 2003). The extracellular domain consists a small region homologous to the collagen-binding domain of fibronectin and of fifteen repeats of approximately 147 amino acid residues. Each of these repeats is homologous to the 157-residue extracytoplasmic domain of the mannose 6-phosphate receptor. Binding to IGF2 is mediated through one of the repeats, while two different repeats are responsible for binding to mannose-6-phosphate. The IGF2R is approximately 300 kDa in size it appears to exist and function as a dimer.

Function

IGF2R functions to clear IGF2 from the cell surface to attenuate signalling, and to transport lysosomal acid hydrolase precursors from the Golgi apparatus to the lysosome. After binding IGF2 at the cell surface, IGF2Rs accumulate in forming clathrin-coated vesicles and are internalized. In the lumen of the trans-Golgi network, the IGF2R binds M6P-tagged cargo (Ghosh, Dahms & Kornfeld 2003). The IGF2Rs (bound to their cargo) are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles (Ghosh & Kornfeld 2004). IGF2Rs from both the cell surface and the Golgi are trafficked to the early endosome where, in the relatively low pH environment of the endosome, the IGF2Rs release their cargo. The IGF2Rs are recycled back to the Golgi, again by way of interaction with GGAs and vesicles. The cargo proteins are then trafficked to the lysosome via the late endosome independently of the IGF2Rs.

References

  • Ghosh, Pradipta; Dahms, Nancy H. & Kornfeld, Stuart (2003), " ", Nature Reviews Molecular and Cell Biology 4: 203-121, PMID 12612639
  • Ghosh, Pradipta & Kornfeld, Stuart (2004), " ", European Journal of Cell Biology 83: 257-262, PMID 15511083

See also

Further reading

  • O'Dell SD, Day IN (1998). "Insulin-like growth factor II (IGF-II).". Int. J. Biochem. Cell Biol. 30 (7): 767-71. PMID 9722981.
  • Hawkes C, Kar S (2004). "The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system.". Brain Res. Brain Res. Rev. 44 (2-3): 117-40. doi:10.1016/j.brainresrev.2003.11.002. PMID 15003389.
  • Scott CD, Firth SM (2005). "The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage disposal?". Horm. Metab. Res. 36 (5): 261-71. doi:10.1055/s-2004-814477. PMID 15156403.
  • Antoniades HN, Galanopoulos T, Neville-Golden J, Maxwell M (1992). "Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry.". Int. J. Cancer 50 (2): 215-22. PMID 1370435.
  • Zhou J, Bondy C (1992). "Insulin-like growth factor-II and its binding proteins in placental development.". Endocrinology 131 (3): 1230-40. PMID 1380437.
  • Morgan DO, Edman JC, Standring DN, et al. (1987). "Insulin-like growth factor II receptor as a multifunctional binding protein.". Nature 329 (6137): 301-7. doi:10.1038/329301a0. PMID 2957598.
  • Oshima A, Nolan CM, Kyle JW, et al. (1988). "The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells.". J. Biol. Chem. 263 (5): 2553-62. PMID 2963003.
  • De Souza AT, Hankins GR, Washington MK, et al. (1996). "M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity.". Nat. Genet. 11 (4): 447-9. doi:10.1038/ng1295-447. PMID 7493029.
  • Ilvesmäki V, Blum WF, Voutilainen R (1994). "Insulin-like growth factor binding proteins in the human adrenal gland.". Mol. Cell. Endocrinol. 97 (1-2): 71-9. PMID 7511544.
  • De Souza AT, Hankins GR, Washington MK, et al. (1995). "Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors.". Oncogene 10 (9): 1725-9. PMID 7753549.
  • Schmidt B, Kiecke-Siemsen C, Waheed A, et al. (1995). "Localization of the insulin-like growth factor II binding site to amino acids 1508-1566 in repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor.". J. Biol. Chem. 270 (25): 14975-82. PMID 7797478.
  • Rao PH, Murty VV, Gaidano G, et al. (1994). "Subregional mapping of 8 single copy loci to chromosome 6 by fluorescence in situ hybridization.". Cytogenet. Cell Genet. 66 (4): 272-3. PMID 8162705.
  • Ishiwata T, Bergmann U, Kornmann M, et al. (1997). "Altered expression of insulin-like growth factor II receptor in human pancreatic cancer.". Pancreas 15 (4): 367-73. PMID 9361090.
  • Tikkanen R, Peltola M, Oinonen C, et al. (1998). "Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase.". EMBO J. 16 (22): 6684-93. doi:10.1093/emboj/16.22.6684. PMID 9362483.
  • Nykjaer A, Christensen EI, Vorum H, et al. (1998). "Mannose 6-phosphate/insulin-like growth factor-II receptor targets the urokinase receptor to lysosomes via a novel binding interaction.". J. Cell Biol. 141 (3): 815-28. PMID 9566979.
  • Díaz E, Pfeffer SR (1998). "TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking.". Cell 93 (3): 433-43. PMID 9590177.
  • Wan L, Molloy SS, Thomas L, et al. (1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization.". Cell 94 (2): 205-16. PMID 9695949.
  • Killian JK, Jirtle RL (1999). "Genomic structure of the human M6P/IGF2 receptor.". Mamm. Genome 10 (1): 74-7. PMID 9892739.
  • Kumar S, Hand AT, Connor JR, et al. (1999). "Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions.". J. Biol. Chem. 274 (24): 17123-31. PMID 10358067.
v • d • e
Receptors: growth factor receptors
Neurotrophin receptorsLow affinity nerve growth factor receptor - high affinity (TrkA, TrkB, TrkC)
Somatomedin receptorInsulin-like growth factor 1 receptor - Insulin-like growth factor 2 receptor
OtherActivin receptor (Type 1, Type 2) - Bone morphogenetic protein receptors - C-MET - CD117 - Erythropoietin receptor - Epidermal growth factor receptor - Fibroblast growth factor receptor - Platelet-derived growth factor receptor - TGF beta receptors - VEGF receptors
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Insulin-like_growth_factor_2_receptor". A list of authors is available in Wikipedia.
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