Identification of domains of the insulin-like growth factor I receptor that are required for protection from apoptosis.

Molecular and Cellular Biology
R O'ConnorW A Blättler

Abstract

Using a series of insulin-like growth factor I (IGF-I) receptor mutants, we have attempted to define domains required for transmitting the antiapoptotic signal from the receptor and to compare these domains with those required for mitogenesis or transformation. In FL5.12 cells transfected with wild-type IGF-I receptors, IGF-I affords protection from interleukin 3 withdrawal but is not mitogenic. An IGF-I receptor lacking a functional ATP binding site provided no protection from apoptosis. However, receptors mutated at tyrosine residue 950 or in the tyrosine cluster (1131, 1135, and 1136) within the kinase domain remained capable of suppressing apoptosis, although such mutations are known to inactivate transforming and mitogenic functions. In the C terminus of the IGF-I receptor, two mutations, one at tyrosine 1251 and one which replaced residues histidine 1293 and lysine 1294, abolished the antiapoptotic function, whereas mutation of the four serines at 1280 to 1283 did not. Interestingly, receptors truncated at the C terminus had enhanced antiapoptotic function. In Rat-1/ c-MycER fibroblasts, the Y950F mutant and the tyrosine cluster mutant could still provide protection from c-Myc-induced apoptosis, whereas mutant Y1250/1251F...Continue Reading

References

Oct 8, 1992·Nature·R P BissonnetteD R Green
Apr 3, 1992·Cell·G I EvanD C Hancock
Nov 1, 1989·Journal of Molecular Endocrinology·K A Freed, A C Herington
Apr 1, 1995·Endocrine Reviews·D LeRoithC T Roberts
Apr 20, 1995·Nature·T ChittendenB C Guild
May 19, 1995·Cell·J L Cleveland, J N Ihle
Jan 1, 1993·Life Sciences·T W Moody, F Cuttitta
Jan 1, 1993·Journal of Cancer Research and Clinical Oncology·U KaiserK Havemann
Jul 16, 1996·Biochemical and Biophysical Research Communications·B Valentinis, R Baserga

❮ Previous
Next ❯

Citations

Jul 9, 1998·The American Journal of Physiology·J F Kuemmerle, T L Bushman
Jan 11, 2000·Journal of Cellular Biochemistry·R Baserga, A Morrione
Jul 15, 2003·Journal of Biomolecular Screening·James HynesDmitri B Papkovsky
Jun 17, 2006·The Tohoku Journal of Experimental Medicine·Shori AbeTakeshi Sasaki
Dec 14, 2006·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Paolo OnoriEugenio Gaudio
Apr 16, 2008·Expert Opinion on Therapeutic Targets·John S P Yuen, Valentine M Macaulay
Aug 12, 2016·The Journal of Biological Chemistry·Rozálie HexnerováLenka Žáková
Sep 24, 2016·Oncotarget·Deeksha VishwamitraHesham M Amin
Oct 22, 2019·American Journal of Clinical Oncology·Neeta K VenepalliArkadiusz Z Dudek
Jun 11, 1999·Immunology and Cell Biology·A J ButtR C Baxter
Mar 27, 1998·Breast Cancer Research and Treatment·L Sepp-Lorenzino
Jun 15, 2004·Cell Death and Differentiation·S SperandioD E Bredesen
Feb 26, 2009·Fetal and Pediatric Pathology·Domenico CoppolaEnid Gilbert-Barness
Apr 1, 1999·Age·K Hubbard, H L Ozer
Jan 21, 2012·EMBO Reports·Dudi WarsitoBita Sehat
Mar 13, 2012·Cancer Biology & Therapy·Yojiro OjimaYuji Hiramatsu
Jul 11, 2012·Journal of Signal Transduction·Barbara P Craddock, W Todd Miller
Nov 20, 2016·G3 : Genes - Genomes - Genetics·David A BulgerMichael W Krause
Mar 15, 2018·Journal of Molecular Endocrinology·Fumihiko Hakuno, Shin-Ichiro Takahashi
Jun 1, 1997·Endocrinology·R Baserga
Feb 28, 1998·The Journal of Biological Chemistry·F BertrandG Cherqui
Mar 27, 1998·Breast Cancer Research and Treatment·A A Rasmussen, K J Cullen
May 30, 1998·The Journal of Biological Chemistry·M ResnicoffR Baserga

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis