Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells

Gary S. Goldberg, David B. Alexander, Patricia Pellicena, Zhong-Yin Zhang, Hiroyuki Tsuda, W. Todd Miller

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of Cas, in a region that is required for binding to a number of other proteins including Crk. We tested synthetic peptides modeled on Cas phosphorylation sites, and found that the sequence containing tyrosine 253 was phosphorylated by Src most efficiently. Using cells derived from Cas-deficient mice, we confirmed that Cas greatly enhanced the ability of Src to transform cells. Phosphorylation of Cas on tyrosine 253 was not required for Src to increase growth rate, suppress contact inhibition, or suppress anchorage dependence. Yet, in contrast to these growth characteristics, phosphorylation of Cas on tyrosine 253 was required for Src to promote cell migration. Thus, a single phosphorylation site on this focal adhesion adaptor protein can effectively separate cell migration from other transformed growth characteristics.

Original languageEnglish (US)
Pages (from-to)46533-46540
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number47
DOIs
StatePublished - Nov 21 2003
Externally publishedYes

Fingerprint

Phosphorylation
Cell Movement
Tyrosine
Focal Adhesions
Adhesion
Growth
Contact Inhibition
Mass spectrometry
Mass Spectrometry
Proteins
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Goldberg, G. S., Alexander, D. B., Pellicena, P., Zhang, Z-Y., Tsuda, H., & Miller, W. T. (2003). Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells. Journal of Biological Chemistry, 278(47), 46533-46540. https://doi.org/10.1074/jbc.M307526200

Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells. / Goldberg, Gary S.; Alexander, David B.; Pellicena, Patricia; Zhang, Zhong-Yin; Tsuda, Hiroyuki; Miller, W. Todd.

In: Journal of Biological Chemistry, Vol. 278, No. 47, 21.11.2003, p. 46533-46540.

Research output: Contribution to journalArticle

Goldberg, GS, Alexander, DB, Pellicena, P, Zhang, Z-Y, Tsuda, H & Miller, WT 2003, 'Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells', Journal of Biological Chemistry, vol. 278, no. 47, pp. 46533-46540. https://doi.org/10.1074/jbc.M307526200
Goldberg, Gary S. ; Alexander, David B. ; Pellicena, Patricia ; Zhang, Zhong-Yin ; Tsuda, Hiroyuki ; Miller, W. Todd. / Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 47. pp. 46533-46540.
@article{379da6f67de9483f8652752ac417480b,
title = "Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells",
abstract = "Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of Cas, in a region that is required for binding to a number of other proteins including Crk. We tested synthetic peptides modeled on Cas phosphorylation sites, and found that the sequence containing tyrosine 253 was phosphorylated by Src most efficiently. Using cells derived from Cas-deficient mice, we confirmed that Cas greatly enhanced the ability of Src to transform cells. Phosphorylation of Cas on tyrosine 253 was not required for Src to increase growth rate, suppress contact inhibition, or suppress anchorage dependence. Yet, in contrast to these growth characteristics, phosphorylation of Cas on tyrosine 253 was required for Src to promote cell migration. Thus, a single phosphorylation site on this focal adhesion adaptor protein can effectively separate cell migration from other transformed growth characteristics.",
author = "Goldberg, {Gary S.} and Alexander, {David B.} and Patricia Pellicena and Zhong-Yin Zhang and Hiroyuki Tsuda and Miller, {W. Todd}",
year = "2003",
month = "11",
day = "21",
doi = "10.1074/jbc.M307526200",
language = "English (US)",
volume = "278",
pages = "46533--46540",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "47",

}

TY - JOUR

T1 - Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells

AU - Goldberg, Gary S.

AU - Alexander, David B.

AU - Pellicena, Patricia

AU - Zhang, Zhong-Yin

AU - Tsuda, Hiroyuki

AU - Miller, W. Todd

PY - 2003/11/21

Y1 - 2003/11/21

N2 - Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of Cas, in a region that is required for binding to a number of other proteins including Crk. We tested synthetic peptides modeled on Cas phosphorylation sites, and found that the sequence containing tyrosine 253 was phosphorylated by Src most efficiently. Using cells derived from Cas-deficient mice, we confirmed that Cas greatly enhanced the ability of Src to transform cells. Phosphorylation of Cas on tyrosine 253 was not required for Src to increase growth rate, suppress contact inhibition, or suppress anchorage dependence. Yet, in contrast to these growth characteristics, phosphorylation of Cas on tyrosine 253 was required for Src to promote cell migration. Thus, a single phosphorylation site on this focal adhesion adaptor protein can effectively separate cell migration from other transformed growth characteristics.

AB - Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of Cas, in a region that is required for binding to a number of other proteins including Crk. We tested synthetic peptides modeled on Cas phosphorylation sites, and found that the sequence containing tyrosine 253 was phosphorylated by Src most efficiently. Using cells derived from Cas-deficient mice, we confirmed that Cas greatly enhanced the ability of Src to transform cells. Phosphorylation of Cas on tyrosine 253 was not required for Src to increase growth rate, suppress contact inhibition, or suppress anchorage dependence. Yet, in contrast to these growth characteristics, phosphorylation of Cas on tyrosine 253 was required for Src to promote cell migration. Thus, a single phosphorylation site on this focal adhesion adaptor protein can effectively separate cell migration from other transformed growth characteristics.

UR - http://www.scopus.com/inward/record.url?scp=0345306687&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345306687&partnerID=8YFLogxK

U2 - 10.1074/jbc.M307526200

DO - 10.1074/jbc.M307526200

M3 - Article

C2 - 12972425

AN - SCOPUS:0345306687

VL - 278

SP - 46533

EP - 46540

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 47

ER -