PMID- 24276851
OWN - NLM
STAT- MEDLINE
DCOM- 20140818
LR  - 20211021
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Print)
IS  - 1420-682X (Linking)
VI  - 71
IP  - 13
DP  - 2014 Jul
TI  - Something old, something new and something borrowed: emerging paradigm of 
      insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation.
PG  - 2403-27
LID - 10.1007/s00018-013-1514-y [doi]
AB  - The insulin-like growth factor type 1 receptor (IGF-1R) plays a key role in the 
      development and progression of cancer; however, therapeutics targeting it have 
      had disappointing results in the clinic. As a receptor tyrosine kinase (RTK), 
      IGF-1R is traditionally described as an ON/OFF system, with ligand stabilizing 
      the ON state and exclusive kinase-dependent signaling activation. Newly added to 
      the traditional model, ubiquitin-mediated receptor downregulation and degradation 
      was originally described as a response to ligand/receptor interaction and thus 
      inseparable from kinase signaling activation. Yet, the classical model has proven 
      over-simplified and insufficient to explain experimental evidence accumulated 
      over the last decade, including kinase-independent signaling, unbalanced 
      signaling, or dissociation between signaling and receptor downregulation. Based 
      on the recent findings that IGF-1R "borrows" components of G-protein coupled 
      receptor (GPCR) signaling, including beta-arrestins and G-protein-related kinases, 
      we discuss the emerging paradigm for the IGF-1R as a functional RTK/GPCR hybrid, 
      which integrates the kinase signaling with the IGF-1R canonical GPCR 
      characteristics. The contradictions to the classical IGF-1R signaling concept as 
      well as the design of anti-IGF-1R therapeutics treatment are considered in the 
      light of this paradigm shift and we advocate recognition of IGF-1R as a valid 
      target for cancer treatment.
FAU - Girnita, Leonard
AU  - Girnita L
AD  - Department of Oncology and Pathology, Cancer Center Karolinska, CCK R8:04, 
      Karolinska Institute, Karolinska University Hospital, 171 76, Stockholm, Sweden, 
      leonard.girnita@ki.se.
FAU - Worrall, Claire
AU  - Worrall C
FAU - Takahashi, Shin-Ichiro
AU  - Takahashi S
FAU - Seregard, Stefan
AU  - Seregard S
FAU - Girnita, Ada
AU  - Girnita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20131126
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (Arrestins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Ubiquitin)
RN  - 0 (beta-Arrestins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Arrestins/genetics/metabolism
MH  - Humans
MH  - *Molecular Targeted Therapy
MH  - Neoplasms/*genetics/pathology/therapy
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphorylation
MH  - Receptor, IGF Type 1/*genetics/metabolism
MH  - Receptors, G-Protein-Coupled/*genetics/metabolism
MH  - Signal Transduction
MH  - Ubiquitin/genetics
MH  - beta-Arrestins
PMC - PMC4055838
EDAT- 2013/11/28 06:00
MHDA- 2014/08/19 06:00
PMCR- 2013/11/26
CRDT- 2013/11/27 06:00
PHST- 2013/05/11 00:00 [received]
PHST- 2013/11/07 00:00 [accepted]
PHST- 2013/10/17 00:00 [revised]
PHST- 2013/11/27 06:00 [entrez]
PHST- 2013/11/28 06:00 [pubmed]
PHST- 2014/08/19 06:00 [medline]
PHST- 2013/11/26 00:00 [pmc-release]
AID - 1514 [pii]
AID - 10.1007/s00018-013-1514-y [doi]
PST - ppublish
SO  - Cell Mol Life Sci. 2014 Jul;71(13):2403-27. doi: 10.1007/s00018-013-1514-y. Epub 
      2013 Nov 26.