PMID- 10391941
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 28
DP  - 1999 Jul 9
TI  - Disruption of coiled-coil domains in Fer protein-tyrosine kinase abolishes
      trimerization but not kinase activation.
PG  - 19934-42
AB  - The protein-tyrosine kinase Fer and the highly homologous proto-oncoprotein
      Fps/Fes are implicated in signaling from a variety of growth factor and cytokine 
      receptors. Here we examine the molecular basis of Fer kinase activation with an
      emphasis on the role of oligomerization. We show that Fer forms trimers in vivo
      and that disruption of either the first or second coiled-coil domain abolishes
      oligomerization, suggesting a cooperative interaction between these two domains. 
      Although Fps/Fes also forms homotypic oligomers, probably via homologous
      coiled-coil domains, no heterotypic interactions were observed between Fer and
      Fps/Fes. Incorporation of catalytically inactive Fer peptides into the oligomeric
      complex caused only mild reduction of wild type Fer kinase activity, suggesting
      that kinase-inactive Fer would not behave as a potent dominant negative. Although
      oligomerization of Fer can potentiate autophosphorylation in trans at three major
      phosphorylation sites, these residues can likely also be phosphorylated in cis.
      In contrast, the testis-specific FerT isomer does not oligomerize and is able to 
      autophosphorylate in cis at two of the same three residues autophosphorylated in 
      Fer. These results suggest that although oligomerization potentiates
      autophosphorylation in trans, this is apparently not necessary for Fer
      activation.
FAU - Craig, A W
AU  - Craig AW
AD  - Cancer Research Laboratories, Queen's University, Kingston, Ontario K7L 3N6,
      Canada.
FAU - Zirngibl, R
AU  - Zirngibl R
FAU - Greer, P
AU  - Greer P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Fusion Proteins, gag-onc)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphopeptides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 110736-90-8 (proto-oncogene protein c-fes-fps)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (v-fps oncogene protein, Fujinami sarcoma virus)
RN  - EC 3.4.21.4 (Trypsin)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Enzyme Activation
MH  - Fusion Proteins, gag-onc/chemistry
MH  - Nuclear Proteins
MH  - Peptide Mapping
MH  - Phosphopeptides/chemistry
MH  - Phosphorylation
MH  - Protein Conformation
MH  - Protein Structure, Secondary
MH  - *Protein-Tyrosine Kinases
MH  - Proto-Oncogene Proteins/*chemistry/genetics/metabolism
MH  - Signal Transduction
MH  - Transfection
MH  - Trypsin
EDAT- 1999/07/03 00:00
MHDA- 1999/07/03 00:01
CRDT- 1999/07/03 00:00
PHST- 1999/07/03 00:00 [pubmed]
PHST- 1999/07/03 00:01 [medline]
PHST- 1999/07/03 00:00 [entrez]
AID - 10.1074/jbc.274.28.19934 [doi]
AID - S0021-9258(19)87116-8 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 9;274(28):19934-42. doi: 10.1074/jbc.274.28.19934.