A Major Site of Tyrosine Phosphorylation Within the SH2 Domain of Fujinami Sarcoma Virus P130gag-fps is Not Required for Protein-tyrosine Kinase Activity or Transforming Potential

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1988 Jun 1

PMID 2452898

Citations 4

Authors

G A Weinmaster

D S Middlemas

T Hunter

Affiliations

Soon will be listed here.

Abstract

Phosphorylation of the major autophosphorylation site (Tyr-1073) within Fujinami sarcoma virus P130gag-fps activates both the intrinsic protein-tyrosine kinase activity and transforming potential of the protein. In this report, a second site of autophosphorylation Tyr-836 was identified. This tyrosine residue is found within a noncatalytic domain (SH2) of P130gag-fps that is required for full protein-kinase activity in both rat and chicken cells. Autophosphorylation of this tyrosine residue implies that the SH2 region lies near the active site in the catalytic domain in the native protein and thus possibly regulates its enzymatic activity. Four mutations have occurred within the SH2 domain between the c-fps and v-fps proteins. Tyr-836 is one of these changes, being a Cys in c-fps. Site-directed mutagenesis was used to investigate the function of this autophosphorylation site. Substitution of Tyr-836 with a Phe had no apparent effect on the transforming ability or protein-tyrosine kinase activity of P130gag-fps in rat-2 cells. Mutagenesis of both autophosphorylation sites (Tyr-1073 and Tyr-836) did not reveal any cooperation between these two phosphorylation sites. The implications of the changes within the SH2 region for v-fps function and activation of the c-fps oncogenic potential are discussed.

Citing Articles

Investigation of the role of P130gag-fps in transformation: generation and use of a temperature-sensitive mutant P130gag-fps.

Weinmaster G, Hunter T J Virol. 1988; 62(10):3849-54.

PMID: 2843679 PMC: 253531. DOI: 10.1128/JVI.62.10.3849-3854.1988.

The common src homology region 2 domain of cytoplasmic signaling proteins is a positive effector of v-fps tyrosine kinase function.

Koch C, Moran M, Sadowski I, Pawson T Mol Cell Biol. 1989; 9(10):4131-40.

PMID: 2685548 PMC: 362491. DOI: 10.1128/mcb.9.10.4131-4140.1989.

Mutation of the serine 312 phosphorylation site does not alter the ability of mouse p53 to inhibit simian virus 40 DNA replication in vivo.

Meek D, Eckhart W J Virol. 1990; 64(4):1734-44.

PMID: 2157055 PMC: 249311. DOI: 10.1128/JVI.64.4.1734-1744.1990.

Cell-specific cyclic AMP-mediated induction of the PDGF receptor.

Weinmaster G, Lemke G EMBO J. 1990; 9(3):915-20.

PMID: 1690127 PMC: 551753. DOI: 10.1002/j.1460-2075.1990.tb08189.x.

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