The cloning of Grb10 reveals a new family of SH2 domain proteins.
SH2 domains function to bind proteins containing phosphotyrosine and are components of proteins that are important signal transducers for tyrosine kinases. We have cloned SH2 domain proteins by screening bacterial expression libraries with the tyrosine phosphorylated carboxyterminus of the epidermal growth factor (EGF) receptor. Here we report the identification of a new SH2 domain protein, Grb10. Grb10 is highly related to Grb7, an SH2 domain protein that we have previously identified. In addition to an SH2 domain, Grb7 and Grb10 have a central domain with similarity to a putative C. elegans gene likely to be involved in neuronal migration. At least three forms of Grb10 exist in fibroblasts apparently due to alternate translational start sites. Grb10 undergoes serine but not tyrosine phosphorylation after EGF treatment resulting in a shift mobility in a large fraction of Grb10 molecules. However Grb10 appears to bind poorly to EGF-Receptor and the true binding partner for the Grb10 SH2 domain is unclear. Grb10 maps to mouse chromosome 11 very close to the EGF-Receptor which is remarkably similar to Grb7 that maps near the EGF-Receptor related HER2 receptor. The finding of multiple family members with evolutionarily conserved domains indicates that these SH2 domain proteins are likely to have an important, although as of yet, unidentified function.
Ooi
J
J
Department of Pharmacology, New York University Medical Center, NY 10016, USA.
Yajnik
V
V
Immanuel
D
D
Gordon
M
M
Moskow
J J
JJ
Buchberg
A M
AM
Margolis
B
B
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D066246:ErbB Receptors / Q000235:genetics; D051383:GRB10 Adaptor Protein; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D012694:Serine / Q000378:metabolism
C495959:Grb10 protein, mouse; D011506:Proteins; D051383:GRB10 Adaptor Protein; D012694:Serine; D066246:ErbB Receptors