Formation of signal transfer complexes between stem cell and platelet-derived growth factor receptors and SH2 domain proteins in vitro

Biochemistry
R HerbstA Ullrich

Abstract

Cellular growth and differentiation signals are generated and defined by the interaction of specific phosphotyrosine residues of activated receptor tyrosine kinases (RTKs) and src homology-2 (SH2) domain-containing intracellular signal transducers. This appears to involve for both the p145c-kit and beta platelet-derived growth factor receptor (PDGF-R) cytoplasmic domains the formation of multiprotein signal transfer complexes, which include combinations of noncatalytic and enzymatically active subunits of phosphatidylinositol 3'-kinase (PI3'-K), phospholipase C-gamma (PLC gamma), and guanosine trisphosphatase activating protein (GAP). In vitro association experiments indicate that PLC gamma and PI3'-K bind the beta PDGF-R simultaneously, while these two SH2 proteins compete for association to p145c-kit binding sites, with p85/PI3'-K exhibiting higher affinity. Interestingly, GAP and p85/PI3'-K binding to distinct p145c-kit phosphotyrosines is cooperative, enhancing formation of a heterotetrameric signaling complex, which may include different combinations of p85 alpha and p85 beta with p110, p112, and p116 by interaction with the same tyrosine 721 docking site. The diversity of molecular interactions observed for PDGF-R and p14...Continue Reading

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·V DuronioJ W Schrader
Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·K MatuokaT Takenawa
Oct 5, 1990·Cell·D E WilliamsH S Boswell
Jan 25, 1991·Cell·L C CantleyS Soltoff
Mar 30, 1990·Science·A KazlauskasJ A Cooper
Apr 20, 1990·Cell·A Ullrich, J Schlessinger
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M F MoranT Pawson
Mar 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M I WahlG Carpenter
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·L Claesson-WelshC H Heldin
Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A M HoneggerJ Schlessinger
Jan 1, 1988·Annual Review of Biochemistry·Y Yarden, A Ullrich

❮ Previous
Next ❯

Citations

Jan 3, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M KroiherR E Steele
Aug 14, 2002·Archives of Insect Biochemistry and Physiology·Marcia J Loeb, Howard Jaffe
Mar 24, 2004·Leukemia Research·Martin Sattler, Ravi Salgia
Sep 18, 1998·Biochimica Et Biophysica Acta·C H HeldinL Rönnstrand
Dec 3, 1999·The International Journal of Biochemistry & Cell Biology·D Linnekin
Jul 1, 1998·Annual Review of Biophysics and Biomolecular Structure·D Bray
Dec 31, 2004·Stem Cells·Johan LennartssonR Shivakrupa
May 27, 2004·Expert Opinion on Therapeutic Targets·Lolita Banerji, Martin Sattler
Jul 30, 2003·Archives of Insect Biochemistry and Physiology·Marcia J LoebGuy Smagghe
Oct 4, 2000·Physiological Reviews·M J Rebecchi, S N Pentyala

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

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.