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The role of cAMP-dependent signaling in receptor-recognized forms of alpha 2-macroglobulin-induced cellular proliferation.

Publication ,  Journal Article
Misra, UK; Akabani, G; Pizzo, SV
Published in: J Biol Chem
September 27, 2002

Ligation of alpha(2)-macroglobulin receptors by receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) activates various signaling cascades and promotes cell proliferation. It also elevates cAMP in murine peritoneal macrophages. We now report that a significant elevation of cAMP-response element-binding protein (CREB) occurs in alpha(2)M*-stimulated cells, and this effect is potentiated by isobutylmethylxanthine, dibutyryl-cAMP, or forskolin. An alpha(2)M* concentration-dependent rapid increase in phosphorylated CREB at Ser(133) also occurred, a necessary event in its activation. Inhibition of Ca(2+)/calmodulin kinase, protein kinases A and C, tyrosine kinases, ribosomal S6 kinase, farnesyl transferase, extracellular signal-regulated kinases 1/2, phosphatidylinositol 3-kinase, or p38 mitogen-activated protein kinase markedly reduce alpha(2)M*-induced phosphorylation of CREB, indicating a role for the p21(ras)-dependent and phosphatidylinositol 3-kinase signaling pathways in regulating CREB activation by alpha(2)M*. Finally, silencing the CREB gene by transfecting cells with a homologous gene sequence double-stranded RNA drastically reduced the expression of CREB and blocked the ability of alpha(2)M* to promote macrophage cell division. We conclude that cAMP-dependent signal transduction as well as other signaling cascades are essential for alpha(2)M*-induced cell proliferation.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 27, 2002

Volume

277

Issue

39

Start / End Page

36509 / 36520

Location

United States

Related Subject Headings

  • ras Proteins
  • alpha-Macroglobulins
  • Transfection
  • Time Factors
  • Thymidine
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Serine
  • SOS1 Protein
 

Citation

APA
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ICMJE
MLA
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Misra, U. K., Akabani, G., & Pizzo, S. V. (2002). The role of cAMP-dependent signaling in receptor-recognized forms of alpha 2-macroglobulin-induced cellular proliferation. J Biol Chem, 277(39), 36509–36520. https://doi.org/10.1074/jbc.M203543200
Misra, Uma Kant, Gamal Akabani, and Salvatore Vincent Pizzo. “The role of cAMP-dependent signaling in receptor-recognized forms of alpha 2-macroglobulin-induced cellular proliferation.J Biol Chem 277, no. 39 (September 27, 2002): 36509–20. https://doi.org/10.1074/jbc.M203543200.
Misra, Uma Kant, et al. “The role of cAMP-dependent signaling in receptor-recognized forms of alpha 2-macroglobulin-induced cellular proliferation.J Biol Chem, vol. 277, no. 39, Sept. 2002, pp. 36509–20. Pubmed, doi:10.1074/jbc.M203543200.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 27, 2002

Volume

277

Issue

39

Start / End Page

36509 / 36520

Location

United States

Related Subject Headings

  • ras Proteins
  • alpha-Macroglobulins
  • Transfection
  • Time Factors
  • Thymidine
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Serine
  • SOS1 Protein