In vivo functional analysis of the Ras exchange factor son of sevenless.
The Son of sevenless (Sos) protein functions as a guanine nucleotide transfer factor for Ras and interacts with the receptor tyrosine kinase Sevenless through the protein Drk, a homolog of mammalian Grb2. In vivo structure-function analysis revealed that the amino terminus of Sos was essential for its function in flies. A molecule lacking the amino terminus was a potent dominant negative. In contrast, a Sos fragment lacking the Drk binding sites was functional and its activity was dependent on the presence of the Sevenless receptor. Furthermore, membrane localization of Sos was independent of Drk. A possible role for Drk as an activator of Sos is discussed and a Drk-independent interaction between Sos and Sevenless is proposed that is likely mediated by the pleckstrin homology domain within the amino terminus.
Karlovich
C A
CA
Department of Biology and Molecular Biology Institute, University of California, Los Angeles 90024, USA.
Bonfini
L
L
McCollam
L
L
Rogge
R D
RD
Daga
A
A
Czech
M P
MP
Banerjee
U
U
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D007301:Insect Hormones / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020664:Son of Sevenless Proteins; D020663:ras Guanine Nucleotide Exchange Factors
D029721:Drosophila Proteins; D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; D007301:Insect Hormones; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D020664:Son of Sevenless Proteins; C080530:drk protein, Drosophila; D020663:ras Guanine Nucleotide Exchange Factors; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila