Son of sevenless binds to the SH3 domain of src-type tyrosine kinase.
To identify molecules which bind to the SH3 domains of p56lck, we screened a mouse T-cell lymphoma cDNA library using the yeast two-hybrid system. As a result, we obtained several positive clones including the Son of Sevenless gene which encodes a mammalian homolog of Drosophila Ras GDP/GTP exchange factor. In a subsequent analysis with the yeast two-hybrid system, Sos associated only with the constitutively active form of p56lck (F505) but not with wild type p56lck (Y505), indicating the requirement for an active conformation of p56lck for binding to Sos. Subsequently, we have demonstrated in vitro that the SH3 domain of p56lck as well as the proline-rich sequences of Sos are responsible for this association. In addition, the proline-rich domain of Sos also bound to the SH3 domains of other src-type tyrosine kinases, src and fyn, but not to that of PLC-gamma. More importantly, the p56lck SH3-Sos interaction was enhanced by serum stimulation, suggesting the possibility that the direct interaction between p56lck SH3 and Sos may contribute to the regulation of the Ras pathway.
Park
C
C
Signal Transduction Laboratory, Mogam Biotechnology Research Institute, Younginsi, Korea.
Choi
Y
Y
Yun
Y
Y
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002457:Cell Extracts / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D019169:Jurkat Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D020663:ras Guanine Nucleotide Exchange Factors; D018909:src Homology Domains
D002457:Cell Extracts; D003470:Culture Media; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)