Insulin-like growth factor 2 receptor

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.

tructure

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 Harv|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 Harv|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 Harv|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

*Citation
last =Ghosh
first =Pradipta
last2 =Dahms
first2 =Nancy H.
last3 =Kornfeld
first3 =Stuart
title =Mannose 6-phosphate receptors: New twists in the tale
journal =Nature Reviews Molecular and Cell Biology
volume =4
pages =203-121
year =2003
pmid = 12612639

*Citation
last =Ghosh
first =Pradipta
last2 =Kornfeld
first2 =Stuart
title =The GGA proteins: key players in protein sorting at the "trans"-Golgi network
journal =European Journal of Cell Biology
volume =83
pages =257-262
year =2004
pmid = 15511083

ee also

* Cluster of differentiation
* IGF-1 Receptor

Further reading

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

External links

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