Src phosphorylates Cas on tyrosine 253 to promote migration of transformed cells.
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.
Goldberg
Gary S
GS
Department of Physiology and Biophysics, School of Medicine, Basic Science Tower T6, Health Science Complex, State University of New York at Stony Brook, Stony Brook, NY 11794-8661, USA. gary.goldberg@stonybrook.edu
Alexander
David B
DB
Pellicena
Patricia
P
Zhang
Zhong-Yin
ZY
Tsuda
Hiroyuki
H
Miller
W Todd
WT
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D002461:Cell Line, Transformed; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D029563:Cellular Apoptosis Susceptibility Protein / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D014443:Tyrosine
D029563:Cellular Apoptosis Susceptibility Protein; D010446:Peptide Fragments; D014443:Tyrosine; D015688:Oncogene Protein pp60(v-src)