Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.54 (
calpain 3
)
430
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
p94
(fer) and
p51
(ferT) are two tyrosine kinases that share identical SH2 and kinase domains but differ in their N-terminal regions. To further explore the cellular functions of these two highly related tyrosine kinases, their subcellular distribution profiles and in vivo phosphorylation activity were followed using double immunofluorescence assay. When combined with immunoprecipitation analysis, this assay showed that
p94
(fer) can lead to the tyrosine phosphorylation and activation of Stat3 but not of Stat1 or Stat2. Native
p94
(fer) exerted this activity when residing in the cytoplasm. However, modified forms of
p94
(fer), which are constitutively nuclear, could also lead to the phosphorylation of Stat3. Endogenous Stat3 and
p94
(fer) co-immunoprecipitated with each other, thus proving the interaction of these two proteins in vivo. Unlike
p94
(fer),
p51
(ferT) did not induce the phosphorylation of Stat3 but led to the phosphorylation of other nuclear proteins. Replacing the unique 43-amino acid-long N-terminal tail of
p51
(ferT) with a parallel segment from the N-terminal tail of
p94
(fer) did not change the subcellular localization of
p51
(ferT) but enabled it to activate Stat3. Thus the different N-terminal sequences of
p94
(fer) and
p51
(ferT) can affect their ability to induce phosphorylation of Stat3 and most probably direct their different cellular functions.
...
PMID:FER kinase activation of Stat3 is determined by the N-terminal sequence. 1087 10
p94
(fer) and
p51
(ferT) are two tyrosine kinases which share identical SH2 and kinase domains but differ in their N-terminal regions. While
p94
(fer) is expressed in most mammalian cells, the accumulation of
p51
(ferT) is restricted to meiotic spermatocytes. Here we show that the different N-terminal tails of
p94
(fer) and
p51
(ferT) direct different autophosphorylation states of these two kinases in vivo. N-terminal coiled-coil domains cooperated to drive the oligomerization and autophosphorylation in trans of
p94
(fer). Moreover, the ectopically expressed N-terminal tail of
p94
(fer) could act as a dominant negative mutant and associated with the endogenous
p94
(fer) protein in CHO cells. This increased significantly the percentage of cells residing in the G0/G1 phase, thus suggesting a role for
p94
(fer) in the regulation of G1 progression. Unlike
p94
(fer), overexpressed
p51
(ferT) was not autophosphorylated in COS1 cells. However, removal of the unique N-terminal 43 aa of
p51
(ferT) or the replacement of this region by a parallel segment from
p94
(fer) endowed the modified
p51
(ferT) with the ability to autophosphorylate. The unique N-terminal sequences of
p51
(ferT) thus interfere with its ability to autophosphorylate in vivo. These experiments indicate that the N-terminal sequences of the FER tyrosine kinases direct their different cellular autophosphorylation states, thereby dictating their different cellular functions.
...
PMID:N-terminal sequences direct the autophosphorylation states of the FER tyrosine kinases in vivo. 1099 46
