Sphingosine 1-Phosphate Stimulates Tyrosine Phosphorylation of Crk

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). SP...

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Published inThe Journal of biological chemistry Vol. 272; no. 26; pp. 16211 - 16215
Main Authors Blakesley, Vicky A., Beitner-Johnson, Dana, Van Brocklyn, James R., Rani, Sheela, Shen-Orr, Zila, Stannard, Bethel S., Spiegel, Sarah, LeRoith, Derek
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 27.06.1997
American Society for Biochemistry and Molecular Biology
Subjects
3T3 Cells
Adaptor Proteins, Signal Transducing
Animals
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
GRB2 Adaptor Protein
Lysophospholipids
Mice
Phosphorylation
Proteins - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-crk
Sphingosine - analogs & derivatives
Sphingosine - pharmacology
src Homology Domains
Tyrosine - metabolism
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Summary: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.
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ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.26.16211