The Relevance of the SIRP Protein Family to Signal Transduction and Cell Adhesion
type: CreativeWork
description: The SIRPs are a recently discovered family of glycoproteins comprising more than 30 members belonging to the immunoglobulin superfamily. The two different structural subtypes, termed SIRP α and SIRP β, are distinguished by the presence or absence of a cytoplasmic domain, respectively. SIRP α1, the first member of the family to be purified, had been characterised as a negative regulator of signal transduction, and transformation assays had suggested that it also had tumour suppressive effects. Little or nothing is known about the possible function of either the other SIRP α homologues or the members of the SIRP β subtype. The Ig-like domains possessed in the extracellular domains of all SIRPs suggest they have binding partners outside the cell. Cell adhesion experiments using the extracellular domains of SIRP family members showed that SIRP α have adhesion molecule properties. This led to the identification of CD47 as one ligand for SIRP α, performed in collaboration with others21and confirmed here. Furthermore, these experiments suggested that SIRP α molecules have at least one further unknown ligand that is not CD47. The discovery that SIRP α was a cell adhesion molecule with a regulatory role in signal transduction was expanded by in vitro kinase experiments and experiments with inhibitors of tyrosine kinases. They showed that SIRP α associated with more than one kinase activity, and that cytosolic tyrosine kinases, probably of the srcfamily, were necessary for SIRP α to regulate tyrosine phosphorylation of a receptor. In contrast to SIRP α molecules, proteins belonging to the SIRP β subtype remain uncharacterised. Therefore a large part of this work concentrates on the SIRP β subtype, its associated proteins, localisation and possible function in a cell. In vitro association experiments revealed that SIRP β is part of a multiprotein complex at the cell membrane, where SIRP β1 interacted with DAP12, an adaptor protein with a transmembrane domain. DAP12 linked SIRP…
abstract: The SIRPs are a recently discovered family of glycoproteins comprising more than 30 members belonging to the immunoglobulin superfamily. The two different structural subtypes, termed SIRP α and SIRP β, are distinguished by the presence or absence of a cytoplasmic domain, respectively. SIRP α1, the first member of the family to be purified, had been characterised as a negative regulator of signal transduction, and transformation assays had suggested that it also had tumour suppressive effects. Little or nothing is known about the possible function of either the other SIRP α homologues or the members of the SIRP β subtype. The Ig-like domains possessed in the extracellular domains of all SIRPs suggest they have binding partners outside the cell. Cell adhesion experiments using the extracellular domains of SIRP family members showed that SIRP α have adhesion molecule properties. This led to the identification of CD47 as one ligand for SIRP α, performed in collaboration with others21and confirmed here. Furthermore, these experiments suggested that SIRP α molecules have at least one further unknown ligand that is not CD47. The discovery that SIRP α was a cell adhesion molecule with a regulatory role in signal transduction was expanded by in vitro kinase experiments and experiments with inhibitors of tyrosine kinases. They showed that SIRP α associated with more than one kinase activity, and that cytosolic tyrosine kinases, probably of the srcfamily, were necessary for SIRP α to regulate tyrosine phosphorylation of a receptor. In contrast to SIRP α molecules, proteins belonging to the SIRP β subtype remain uncharacterised. Therefore a large part of this work concentrates on the SIRP β subtype, its associated proteins, localisation and possible function in a cell. In vitro association experiments revealed that SIRP β is part of a multiprotein complex at the cell membrane, where SIRP β1 interacted with DAP12, an adaptor protein with a transmembrane domain. DAP12 linked SIRP…
author: Cant, Charles Alexander
date published: 2001-12-19
date modified: 2026-07-24T02:51:21Z
provider: Ludwig Maxmilians Universität München
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Ludwig-Maximilians-Universität