Sphingosine 1-phosphate stimulates tyrosine phosphorylation of Crk

Vicky A. Blakesley, Dana Beitner-Johnson, James R. Van Brooklyn, Sheela Rani, Zila Shen-Orr, Bethel S. Stannard, Sarah Spiegel, Derek LeRoith

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


The proto-oncogene molecule c-Crk plays a role in growth factor-induced activation of Ras. Sphingosine 1-phosphate (SPP), a metabolite of cellular sphingolipids, has previously been shown to play a role in growth factor receptor signaling (Olivera, A., and Spiegel, S. (1993) Nature 365, 557- 560). SPP was found to strongly induce tyrosine phosphorylation of Crk, but not Shc, in NIH-3T3 parental, insulin-like growth factor-I receptor- overexpressing and Crk-overexpressing (3T3-Crk) fibroblasts. Sphingosine, a metabolic precursor of SPP, also produced a slight increase in tyrosine phosphorylation of Crk. In contrast, other sphingolipid metabolites including ceramide did not alter Crk tyrosine phosphorylation. Furthermore, Crk enhanced SPP-induced mitogenesis, as measured by SPP-stimulated [3H]thymidine incorporation in a manner proportional to the level of Crk expression in 3T3-Crk cells. This stimulation appears to be Ras-dependent, whereas SPP stimulation of MAP kinase activity is Ras-independent. These data indicate that SPP activates a tyrosine kinase that phosphorylates Crk and that Crk is a positive effector of SPP-induced mitogenesis.

Original languageEnglish
Pages (from-to)16211-16215
Number of pages5
JournalJournal of Biological Chemistry
Issue number26
StatePublished - 27 Jun 1997
Externally publishedYes


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