Sequence of rat liver alpha 2-macroglobulin and acute phase control of its messenger RNA.

Gehring, Michael R.; Shiels, Brian; Northemann, Wolfgang; Bruijn, M.H.L. de; Kan, Chen‐Chen; Chain, A C; Noonan, Daniel J.; Fey, Georg H.

doi:10.1016/s0021-9258(19)75947-x

Cited by 174 publications

(2 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…α 2 M is the sixth most abundant plasma protein 23 (2.1 mg/mL 24 ); it is also present in cerebrospinal fluid at low levels (1.0–3.6 μg/mL 25 ). The plasma concentration of α 2 M increases during inflammatory responses in mice 26 . The molecular mechanism underlying the protease inhibitor effects of α 2 M has been widely studied 21 .…”

Section: Introductionmentioning

confidence: 96%

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

Tomihari

Kiyota

Matsuura

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Proteostasis regulates protein folding and degradation; its maintenance is essential for resistance to stress and aging. The loss of proteostasis is associated with many age-related diseases. Within the cell, molecular chaperones facilitate the refolding of misfolded proteins into their bioactive forms, thus preventing undesirable interactions and aggregation. Although the mechanisms of intracellular protein degradation pathways for intracellular misfolded proteins have been extensively studied, the protein degradation pathway for extracellular proteins remain poorly understood. In this study, we identified several misfolded proteins that are substrates for alpha 2-macroglobulin (α2M), an extracellular chaperone. We also established a lysosomal internalization assay for α2M, which revealed that α2M mediates the lysosomal degradation of extracellular misfolded proteins. Comparative analyses of α2M and clusterin, another extracellular chaperone, indicated that α2M preferentially targets aggregation-prone proteins. Thus, we present the degradation pathway of α2M, which interacts with aggregation-prone proteins for lysosomal degradation via selective internalization.

show abstract

Section: Introductionmentioning

confidence: 96%

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

Tomihari

Kiyota

Matsuura

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The complement system is of central importance for immunity and complement 3 ( C3 ) is at the core of its function ( 1 – 3 ). C3 belongs to the thioester bond containing protein (TEP) superfamily ( 4 ) that also includes α 2 -macroglobulin (A2M) ( 5 ), pregnancy zone protein (PZP) ( 6 ), CD109 ( 7 ) and PZP-like A2M domain-containing 8 (CPAMD8) ( 8 ). The appearance and differentiation of C3, A2M and CD109 occurred after the divergence of the sponges and before the divergence of cnidaria from the bilaterian lineage ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Domain-Dependent Evolution Explains Functional Homology of Protostome and Deuterostome Complement C3-Like Proteins

Peng

Cardoso

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Complement proteins emerged early in evolution but outside the vertebrate clade they are poorly characterized. An evolutionary model of C3 family members revealed that in contrast to vertebrates the evolutionary trajectory of C3-like genes in cnidarian, protostomes and invertebrate deuterostomes was highly divergent due to independent lineage and species-specific duplications. The deduced C3-like and vertebrate C3, C4 and C5 proteins had low sequence conservation, but extraordinarily high structural conservation and 2-chain and 3-chain protein isoforms repeatedly emerged. Functional characterization of three C3-like isoforms in a bivalve representative revealed that in common with vertebrates complement proteins they were cleaved into two subunits, b and a, and the latter regulated inflammation-related genes, chemotaxis and phagocytosis. Changes within the thioester bond cleavage sites and the a-subunit protein (ANATO domain) explained the functional differentiation of bivalve C3-like. The emergence of domain-related functions early during evolution explains the overlapping functions of bivalve C3-like and vertebrate C3, C4 and C5, despite low sequence conservation and indicates that evolutionary pressure acted to conserve protein domain organization rather than the primary sequence.

show abstract

Molecular evolution of the vertebrate immune system

Hughes

Yeager

1997

BioEssays

View full text Add to dashboard Cite

Adaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to the divergence of C3 and C4, which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC-linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid level.

show abstract

Sequence of rat liver alpha 2-macroglobulin and acute phase control of its messenger RNA.

Cited by 174 publications

References 53 publications

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

Domain-Dependent Evolution Explains Functional Homology of Protostome and Deuterostome Complement C3-Like Proteins

Molecular evolution of the vertebrate immune system

Contact Info

Product

Resources

About