Src-like adaptor protein (Slap) is a negative regulator of mitogenesis

Serge Roche, Gema Alonso, Andrius Kazlauskas, Vishva M. Dixit, Sara Courtneidge, Akhilesh Pandey

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The Src-like adaptor protein (Slap) is a recently identified adaptor protein containing Src homology 3 (SH3) and SH2 domains. Slap is found in a wide range of cell types and was shown to interact with the Eck receptor tyrosine kinase in a yeast two-hybrid interaction screen. Here, we found that Slap is expressed in NIH3T3 cells and could associate with the activated platelet-derived growth factor (PDGF) receptor. Using mutated versions of the PDGF receptor and phosphopeptide competition experiments, we determined that Slap has the highest affinity for the Src-binding site of the PDGF receptor. Our inability to produce cell lines that stably expressed Slap suggested that Slap inhibited cell growth. We further investigated this issue by transiently expressing Slap by microinjection. Overexpression of Slap by this method inhibited DNA synthesis induced by PDGF and serum, whereas overexpression of the adaptor proteins Grb2 and Shc did not. Finally, microinjection of a Slap antibody into NIH3T3 cells that had been stimulated with suboptimal doses of growth factors potentiated the effects of the growth factors. These data suggest that, unlike other adaptor proteins, Slap is a negative regulator of signalling initiated by growth factors.

Original languageEnglish (US)
Pages (from-to)975-978
Number of pages4
JournalCurrent Biology
Volume8
Issue number17
StatePublished - Aug 27 1998
Externally publishedYes

Fingerprint

Proteins
proteins
Platelet-Derived Growth Factor Receptors
growth factors
Intercellular Signaling Peptides and Proteins
src Homology Domains
Microinjections
mitogenesis
Shc Signaling Adaptor Proteins
Phosphopeptides
platelet-derived growth factor
Platelet-Derived Growth Factor
Receptor Protein-Tyrosine Kinases
Cell growth
cells
Yeast
tyrosine
binding sites
cell growth
Yeasts

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Roche, S., Alonso, G., Kazlauskas, A., Dixit, V. M., Courtneidge, S., & Pandey, A. (1998). Src-like adaptor protein (Slap) is a negative regulator of mitogenesis. Current Biology, 8(17), 975-978.

Src-like adaptor protein (Slap) is a negative regulator of mitogenesis. / Roche, Serge; Alonso, Gema; Kazlauskas, Andrius; Dixit, Vishva M.; Courtneidge, Sara; Pandey, Akhilesh.

In: Current Biology, Vol. 8, No. 17, 27.08.1998, p. 975-978.

Research output: Contribution to journalArticle

Roche, S, Alonso, G, Kazlauskas, A, Dixit, VM, Courtneidge, S & Pandey, A 1998, 'Src-like adaptor protein (Slap) is a negative regulator of mitogenesis', Current Biology, vol. 8, no. 17, pp. 975-978.
Roche S, Alonso G, Kazlauskas A, Dixit VM, Courtneidge S, Pandey A. Src-like adaptor protein (Slap) is a negative regulator of mitogenesis. Current Biology. 1998 Aug 27;8(17):975-978.
Roche, Serge ; Alonso, Gema ; Kazlauskas, Andrius ; Dixit, Vishva M. ; Courtneidge, Sara ; Pandey, Akhilesh. / Src-like adaptor protein (Slap) is a negative regulator of mitogenesis. In: Current Biology. 1998 ; Vol. 8, No. 17. pp. 975-978.
@article{a73fe475dc7b43e7907aebb24bd1f3a1,
title = "Src-like adaptor protein (Slap) is a negative regulator of mitogenesis",
abstract = "The Src-like adaptor protein (Slap) is a recently identified adaptor protein containing Src homology 3 (SH3) and SH2 domains. Slap is found in a wide range of cell types and was shown to interact with the Eck receptor tyrosine kinase in a yeast two-hybrid interaction screen. Here, we found that Slap is expressed in NIH3T3 cells and could associate with the activated platelet-derived growth factor (PDGF) receptor. Using mutated versions of the PDGF receptor and phosphopeptide competition experiments, we determined that Slap has the highest affinity for the Src-binding site of the PDGF receptor. Our inability to produce cell lines that stably expressed Slap suggested that Slap inhibited cell growth. We further investigated this issue by transiently expressing Slap by microinjection. Overexpression of Slap by this method inhibited DNA synthesis induced by PDGF and serum, whereas overexpression of the adaptor proteins Grb2 and Shc did not. Finally, microinjection of a Slap antibody into NIH3T3 cells that had been stimulated with suboptimal doses of growth factors potentiated the effects of the growth factors. These data suggest that, unlike other adaptor proteins, Slap is a negative regulator of signalling initiated by growth factors.",
author = "Serge Roche and Gema Alonso and Andrius Kazlauskas and Dixit, {Vishva M.} and Sara Courtneidge and Akhilesh Pandey",
year = "1998",
month = "8",
day = "27",
language = "English (US)",
volume = "8",
pages = "975--978",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "17",

}

TY - JOUR

T1 - Src-like adaptor protein (Slap) is a negative regulator of mitogenesis

AU - Roche, Serge

AU - Alonso, Gema

AU - Kazlauskas, Andrius

AU - Dixit, Vishva M.

AU - Courtneidge, Sara

AU - Pandey, Akhilesh

PY - 1998/8/27

Y1 - 1998/8/27

N2 - The Src-like adaptor protein (Slap) is a recently identified adaptor protein containing Src homology 3 (SH3) and SH2 domains. Slap is found in a wide range of cell types and was shown to interact with the Eck receptor tyrosine kinase in a yeast two-hybrid interaction screen. Here, we found that Slap is expressed in NIH3T3 cells and could associate with the activated platelet-derived growth factor (PDGF) receptor. Using mutated versions of the PDGF receptor and phosphopeptide competition experiments, we determined that Slap has the highest affinity for the Src-binding site of the PDGF receptor. Our inability to produce cell lines that stably expressed Slap suggested that Slap inhibited cell growth. We further investigated this issue by transiently expressing Slap by microinjection. Overexpression of Slap by this method inhibited DNA synthesis induced by PDGF and serum, whereas overexpression of the adaptor proteins Grb2 and Shc did not. Finally, microinjection of a Slap antibody into NIH3T3 cells that had been stimulated with suboptimal doses of growth factors potentiated the effects of the growth factors. These data suggest that, unlike other adaptor proteins, Slap is a negative regulator of signalling initiated by growth factors.

AB - The Src-like adaptor protein (Slap) is a recently identified adaptor protein containing Src homology 3 (SH3) and SH2 domains. Slap is found in a wide range of cell types and was shown to interact with the Eck receptor tyrosine kinase in a yeast two-hybrid interaction screen. Here, we found that Slap is expressed in NIH3T3 cells and could associate with the activated platelet-derived growth factor (PDGF) receptor. Using mutated versions of the PDGF receptor and phosphopeptide competition experiments, we determined that Slap has the highest affinity for the Src-binding site of the PDGF receptor. Our inability to produce cell lines that stably expressed Slap suggested that Slap inhibited cell growth. We further investigated this issue by transiently expressing Slap by microinjection. Overexpression of Slap by this method inhibited DNA synthesis induced by PDGF and serum, whereas overexpression of the adaptor proteins Grb2 and Shc did not. Finally, microinjection of a Slap antibody into NIH3T3 cells that had been stimulated with suboptimal doses of growth factors potentiated the effects of the growth factors. These data suggest that, unlike other adaptor proteins, Slap is a negative regulator of signalling initiated by growth factors.

UR - http://www.scopus.com/inward/record.url?scp=0032572806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032572806&partnerID=8YFLogxK

M3 - Article

C2 - 9742401

AN - SCOPUS:0032572806

VL - 8

SP - 975

EP - 978

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 17

ER -