Intersectin can regulate the Ras/MAP kinase pathway independent of its role in endocytosis

Xin Kang Tong, Natasha K. Hussain, Anthony G. Adams, John P. O'Bryan, Peter S. McPherson

Research output: Contribution to journalArticle

Abstract

We previously identified intersectin, a multiple EH and SH3 domain-containing protein, as a component of the endocytic machinery. Overexpression of the SH3 domains of intersectin blocks transferrin receptor endocytosis, possibly by disrupting targeting of accessory proteins of clathrin-coated pit formation. More recently, we identified mammalian Sos, a guanine-nucleotide exchange factor for Ras, as an intersectin SH3 domain-binding partner. We now demonstrate that overexpression of intersectin's SH3 domains blocks activation of Ras and MAP kinase in various cell lines. Several studies suggest that activation of MAP kinase downstream of multiple receptor types is dependent on endocytosis. Thus, the dominant-negative effect of the SH3 domains on Ras/MAP kinase activation may be indirectly mediated through a block in endocytosis. Consistent with this idea, incubating cells at 4 °C or with phenylarsine oxide, treatments previously established to inhibit EGF receptor endocytosis, blocks EGF-dependent activation of MAP kinase. However, under these conditions, Ras activity is unaffected and overexpression of the SH3 domains of intersectin is still able to block Ras activation. Thus, intersectin SH3 domain overexpression can effect EGF-mediated MAP kinase activation directly through a block in Ras, consistent with a functional role for intersectin in Ras activation.

Original languageEnglish (US)
Pages (from-to)29894-29899
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number38
DOIs
StatePublished - Sep 22 2000
Externally publishedYes

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src Homology Domains
Endocytosis
Phosphotransferases
Chemical activation
Epidermal Growth Factor
ras Guanine Nucleotide Exchange Factors
Clathrin
Transferrin Receptors
Accessories
Protein Transport
intersectin 1
Epidermal Growth Factor Receptor
Machinery
Proteins
Cells
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tong, X. K., Hussain, N. K., Adams, A. G., O'Bryan, J. P., & McPherson, P. S. (2000). Intersectin can regulate the Ras/MAP kinase pathway independent of its role in endocytosis. Journal of Biological Chemistry, 275(38), 29894-29899. https://doi.org/10.1074/jbc.M004096200

Intersectin can regulate the Ras/MAP kinase pathway independent of its role in endocytosis. / Tong, Xin Kang; Hussain, Natasha K.; Adams, Anthony G.; O'Bryan, John P.; McPherson, Peter S.

In: Journal of Biological Chemistry, Vol. 275, No. 38, 22.09.2000, p. 29894-29899.

Research output: Contribution to journalArticle

Tong, XK, Hussain, NK, Adams, AG, O'Bryan, JP & McPherson, PS 2000, 'Intersectin can regulate the Ras/MAP kinase pathway independent of its role in endocytosis', Journal of Biological Chemistry, vol. 275, no. 38, pp. 29894-29899. https://doi.org/10.1074/jbc.M004096200
Tong, Xin Kang ; Hussain, Natasha K. ; Adams, Anthony G. ; O'Bryan, John P. ; McPherson, Peter S. / Intersectin can regulate the Ras/MAP kinase pathway independent of its role in endocytosis. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 38. pp. 29894-29899.
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