Conserved hydrophobicity in the SH2-kinase linker is required for catalytic activity of Csk and CHK.
The crystal structure of full-length Csk (C-terminal Src kinase) molecules shows a hydrophobic interaction between the SH2-kinase linker residue Phe183 and the alphaC-helix of the catalytic domain. To study the possible involvement of this contact in the regulation of the activity of Csk and CHK (Csk homologous kinase), a Csk SH2-kinase linker deletion mutant, Csk Phe183 and CHK Leu223 point mutants were analyzed. It was observed that a residue with a long hydrophobic side chain in position 183 (Csk) and 223 (CHK) is required to sustain the catalytic activity of Csk and CHK. These results suggest that Csk Phe183 and CHK Leu223 stabilize the movement of the alphaC-helix of these protein tyrosine kinases.
Mikkola
Esa T
ET
Division of Biochemistry, Department of Biosciences, P.O. Box 56, 00014 University of Helsinki, Finland. esa.t.mikkola@helsinki.fi
Bergman
Mathias
M
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D000081247:CSK Tyrosine-Protein Kinase; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D016392:Proto-Oncogene Proteins pp60(c-src); D014162:Transfection; D014443:Tyrosine / Q000737:chemistry; D014633:Valine / Q000737:chemistry; D018909:src Homology Domains; D019061:src-Family Kinases
D014443:Tyrosine; D010649:Phenylalanine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C085377:MATK protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; C000631346:CSK protein, human; D007930:Leucine; D014633:Valine; D000409:Alanine