Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity
- PMID: 2577868
Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity
Abstract
The catalytic domains of protein-tyrosine kinases such as the P130gag-fps oncoprotein contain the sequence HRDLAARN, followed thirteen residues C-terminal by DFG (P130gag-fps residues 1041-1048 and 1061-1063). These residues define a structural motif conserved among eucaryotic protein kinases (-RD----N, DFG) and shared with several procaryotic 3'aminoglycoside phosphotransferases (H-D----N, D-G). Functional analysis of mutant v-fps proteins employing bacterial and mammalian expression systems indicated that this motif is critical for P130gag-fps kinase activity and oncogenicity. In particular, conservative substitutions of the two invariant aspartates (asp1043, asp1061) with glutamate or asparagine completely eliminated enzymatic activity, suggesting that these residues are essential for catalysis. In contrast, substitution of arg1042 with glutamate decreased but did not eliminate v-fps kinase activity in bacteria. The effects of these and other amino acid substitutions within the phosphotransfer motif and at the nearby autophosphorylation site (tyr1073) of P130gag-fps indicate that these conserved residues are intrinsically essential to the execution or regulation of catalytic activity, and suggest that tight spatial constraints operate within the active centre of the v-fps tyrosine kinase domain.
Similar articles
-
Leucine zipper-like domain regulates the autophosphorylation and the transforming activity of P130gag-fps.Biochem Biophys Res Commun. 1995 Jun 15;211(2):447-53. doi: 10.1006/bbrc.1995.1834. Biochem Biophys Res Commun. 1995. PMID: 7794256
-
Catalytic and non-catalytic domains of the Fujinami sarcoma virus P130gag-fps protein-tyrosine kinase distinguished by the expression of v-fps polypeptides in Escherichia coli.Oncogene. 1987 May;1(2):181-91. Oncogene. 1987. PMID: 2449646
-
Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned using anti-phosphotyrosine antibody.Oncogene. 1988 Dec;3(6):621-7. Oncogene. 1988. PMID: 2485255
-
A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps.Mol Cell Biol. 1986 Dec;6(12):4396-408. doi: 10.1128/mcb.6.12.4396-4408.1986. Mol Cell Biol. 1986. PMID: 3025655 Free PMC article.
-
Structure-function relationships in cellular and viral fps/fes cytoplasmic protein-tyrosine kinases.Adv Exp Med Biol. 1988;234:55-64. doi: 10.1007/978-1-4757-1980-2_5. Adv Exp Med Biol. 1988. PMID: 3063089 Review. No abstract available.
Cited by
-
The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory.eNeuro. 2017 Feb 20;4(1):ENEURO.0212-16.2017. doi: 10.1523/ENEURO.0212-16.2017. eCollection 2017 Jan-Feb. eNeuro. 2017. PMID: 28275711 Free PMC article.
-
Efficient motif search in ranked lists and applications to variable gap motifs.Nucleic Acids Res. 2012 Jul;40(13):5832-47. doi: 10.1093/nar/gks206. Epub 2012 Mar 13. Nucleic Acids Res. 2012. PMID: 22416066 Free PMC article.
-
The triplet puzzle of homologies in receptor heteromers exists also in other types of protein-protein interactions.J Mol Neurosci. 2011 Jul;44(3):173-7. doi: 10.1007/s12031-011-9511-9. Epub 2011 Mar 18. J Mol Neurosci. 2011. PMID: 21416272
-
Triplet puzzle: homologies of receptor heteromers.J Mol Neurosci. 2010 Jun;41(2):294-303. doi: 10.1007/s12031-009-9313-5. Epub 2009 Dec 4. J Mol Neurosci. 2010. PMID: 19960372
-
Characterization of a eukaryotic-like tyrosine protein kinase expressed by the Shiga toxin-encoding bacteriophage 933W.J Bacteriol. 2004 Jun;186(11):3472-9. doi: 10.1128/JB.186.11.3472-3479.2004. J Bacteriol. 2004. PMID: 15150234 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Miscellaneous