Mechanisms of lysolipid phosphate effects on cellular survival and proliferation

Edward J. Goetzl, Hsinyu Lee, Hana Dolezalova, Kimberly R. Kalli, Cheryl A Conover, Yu Long Hu, Toshi Azuma, Thomas P. Stossel, Joel S. Karliner, Robert B. Jaffe

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Abstract

The specificity of cellular effects of lysolipid phosphate (LLP) growth factors is determined by binding to endothelial differentiation gene-encoded G protein-coupled receptors (EDG Rs), which transduce diverse proliferative and effector signals. The primary determinants of cellular responses to LLPs are the generative and biodegradative events, which establish steady-state concentrations of each LLP at cell surfaces, and the relative frequency of expression of each EDG R. There are major differences among types of cells in the net effective generation of the LLPs, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), and in their profile of expression of EDG Rs. The less well characterized secondary determinants of cellular specificity of LLPs are high-affinity binding proteins with carrier and cell-presentation functions, cell-selective regulators of expression of EDG Rs, and cellular factors that govern coupling of EDG Rs to G protein transductional pathways. The roles of components of the LLP-EDG R system in normal physiology and disease processes will be definitively elucidated only after development of animal models with biologically meaningful alterations in genes encoding EDG Rs and the discovery of potent and selective pharmacological probes.

Original languageEnglish (US)
Pages (from-to)177-187
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume905
StatePublished - 2000

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G-Protein-Coupled Receptors
Phosphates
Cell Proliferation
Gene encoding
Physiology
GTP-Binding Proteins
Genes
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Animals
Animal Models
Pharmacology
Phosphate
Protein
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Goetzl, E. J., Lee, H., Dolezalova, H., Kalli, K. R., Conover, C. A., Hu, Y. L., ... Jaffe, R. B. (2000). Mechanisms of lysolipid phosphate effects on cellular survival and proliferation. Annals of the New York Academy of Sciences, 905, 177-187.

Mechanisms of lysolipid phosphate effects on cellular survival and proliferation. / Goetzl, Edward J.; Lee, Hsinyu; Dolezalova, Hana; Kalli, Kimberly R.; Conover, Cheryl A; Hu, Yu Long; Azuma, Toshi; Stossel, Thomas P.; Karliner, Joel S.; Jaffe, Robert B.

In: Annals of the New York Academy of Sciences, Vol. 905, 2000, p. 177-187.

Research output: Contribution to journalArticle

Goetzl, EJ, Lee, H, Dolezalova, H, Kalli, KR, Conover, CA, Hu, YL, Azuma, T, Stossel, TP, Karliner, JS & Jaffe, RB 2000, 'Mechanisms of lysolipid phosphate effects on cellular survival and proliferation', Annals of the New York Academy of Sciences, vol. 905, pp. 177-187.
Goetzl, Edward J. ; Lee, Hsinyu ; Dolezalova, Hana ; Kalli, Kimberly R. ; Conover, Cheryl A ; Hu, Yu Long ; Azuma, Toshi ; Stossel, Thomas P. ; Karliner, Joel S. ; Jaffe, Robert B. / Mechanisms of lysolipid phosphate effects on cellular survival and proliferation. In: Annals of the New York Academy of Sciences. 2000 ; Vol. 905. pp. 177-187.
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