Regulation of c-Fgr protein kinase by c-Src kinase (CSK) and by polycationic effectors.
The protein tyrosine kinase expressed by the protooncogene c-fgr is phosphorylated and down-regulated in vitro by the c-Src kinase (CSK). CSK catalyzed phosphorylation affects Tyr-511 of c-Fgr, homologous to Tyr-527 of c-Src and it prevents the autophosphorylation normally occurring at c-Fgr Tyr-400, homologous to c-Src Tyr-416. Polylysine, histones H1 and H2A and other polycationic proteins on the other hand stimulate c-Fgr activity while promoting enhanced autophosphorylation of both Tyr-400 and Tyr-511. Once phosphorylated at Tyr-511 and down-regulated by CSK, c-Fgr is no more susceptible to polylysine stimulation. Previous autophosphorylation (at Tyr-400) reduces c-Fgr susceptibility to down-regulation by CSK, although Tyr-511 can be still phosphorylated by it. If a more exhaustive autophosphorylation (of both Tyr-400 and Tyr-511) is performed in the presence of polylysine, c-Fgr becomes totally insensitive to CSK down-regulation. These data support the concept that down-regulation of c-Fgr by Tyr-511 phosphorylation is prevented if Tyr-400 is also phosphorylated and they are consistent with an outcompetition of phospho-Tyr-511 from the Src homology 2 domain by phospho-Tyr-400, which, in c-Fgr, is surrounded by an amino acid sequence divergent from that of the other Src-related protein tyrosine kinases.
Ruzzene
M
M
Dipartimento di Chimica Biologica, Università di Padova, Italy.
James
P
P
Brunati
A M
AM
Donella-Deana
A
A
Pinna
L A
LA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D008961:Models, Structural; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000737:chemistry / Q000302:isolation & purification; D010766:Phosphorylation; D011107:Polylysine / Q000494:pharmacology*; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D011519:Proto-Oncogenes; D051381:Rats; D013154:Spleen / Q000201:enzymology; D014357:Trypsin; D019061:src-Family Kinases
D000345:Affinity Labels; D010446:Peptide Fragments; D010748:Phosphopeptides; D011518:Proto-Oncogene Proteins; D011107:Polylysine; C010959:5'-(4-fluorosulfonylbenzoyl)adenosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016392:Proto-Oncogene Proteins pp60(c-src); C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; D014357:Trypsin; D000241:Adenosine