Ligation of the alpha2M signaling receptor with receptor-recognized forms of alpha2-macroglobulin initiates protein and DNA synthesis in macrophages. The effect of intracellular calcium.

Published

Journal Article

We have previously reported that receptor-recognized forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M) bind to a distinct receptor (alpha2MSR), Kd approximately 50-100 pM, activating a signaling cascade, triggering tyrosine phosphorylation of phospholipase Cgamma1, and raising cytosolic pH. We have now studied the effects of alpha2M or a cloned and expressed receptor binding fragment (RBF) on protein and DNA synthesis by macrophages. A nearly linear increase in total protein and DNA synthesis was noted at ligand concentrations up to 100 pM; thereafter, synthesis plateaued. The increase (1.5-2-fold) in protein and DNA synthesis was similar to that observed with known growth factors such as epidermal growth factor and platelet derived growth factor. Mutants of RBF which bind well to alpha2MSR, also caused a similar increase in DNA synthesis. By contrast, mutant K1374R which binds poorly to alpha2MSR demonstrated much less of an effect on DNA synthesis. Chelation of intracellular Ca2+ drastically reduced protein and DNA synthesis induced by RBF or the human growth factors. These studies suggest that activation of native alpha2M, such as would occur during tissue injury, produces a molecule with properties which are similar to growth factors.

Full Text

Duke Authors

Cited Authors

  • Misra, UK; Pizzo, SV

Published Date

  • January 1998

Published In

Volume / Issue

  • 1401 / 1

Start / End Page

  • 121 - 128

PubMed ID

  • 9459492

Pubmed Central ID

  • 9459492

Electronic International Standard Serial Number (EISSN)

  • 1878-2434

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/s0167-4889(97)00123-7

Language

  • eng