Mouse anti-Human GRB10 polyclonal antibody

The Shaker family K+ channel protein, Kv1.3, is tyrosine phosphorylated by v-Src kinase at Tyr(137) and Tyr(449) to modulate current magnitude and kinetic properties. Despite two proline rich sequences and these phosphotyrosines contained in the carboxyl and amino terminals of the channel, v-Src kinase fails to co-immunoprecipitate with Kv1.3 as expressed in HEK 293 cells, indicating a lack of direct Src homology 3- or Src homology 2-mediated protein-protein interaction between the channel and the kinase. We show that the adaptor proteins, n-Shc and Grb10, are expressed in the olfactory bulb, a region of the brain where Kv1.3 is highly expressed. In HEK 293 cells, co-expression of Kv1.3 plus v-Src with Grb10 causes a decrease in v-Src-induced Kv1.3 tyrosine phosphorylation and a reversal of v-Src-induced Kv1.3 current suppression, increase in inactivation time constant (tau(inact)), and disruption of cumulative inactivation properties. Co-expression of Kv1.3 plus v-Src with n-Shc did not significantly alter v-Src-induced Kv1.3 current suppression but reversed v-Src induced increased tau(inact) and restored the right-shifted voltage at half-activation (V-1/2) induced by v-Src. The v-Src-induced shift in V and increased tau(inact) was retained when Tyr(220), Tyr(221), and Tyr(304) in the CH domain of n-Shc were mutated to Phe (triple She mutant) but was reversed back to control values when either wildtype She or the family member Sck, which is not a substrate for Src kinase, was substituted for the triple She mutant. Thus the portion of the CH domain that includes Tyr(220), Tyr(221), and Tyr(304) may regulate a shift in Kv1.3 voltage dependence and inactivation kinetics produced by n-Shc in the presence of v-Src. Collectively these data indicate that Grb10 and n-Shc adaptor molecules differentially modulate the degree of Kv1.3 tyrosine phosphorylation, the channel's biophysical properties, and the physical complexes associated with Kv1.3 in the presence of Src kinase.

Head size is important economic trait for many aquaculture fish which is directly linked to their carcass yield. The genetic basis of head size trait remains unclear in many widely cultured fish species. Common carp (Cyprinus carpio) is one of the most widely studied fish due to its importance on both economic and environmental aspects. In this study, we performed genome-wide association study using 433 Yellow River carp individuals from multiple families to identify loci and genes potentially associated with head size related traits including head length (HL), head length/body length ratio (HBR), eye diameter (ED), and eye cross (EC). QTL mapping was utilized to filter the effects of population stratification and improve power for the candidates identification in the largest surveyed family with a published genetic linkage map. Twelve SNPs showed significant for head size traits in GWAS and 18 QTLs were identified in QTL mapping. Our study combining both GWAS and QTL mapping could compensate the deficiency from each other and advance our understanding of head size traits in common carp. To acquire a better understanding of the correlation between head size and body growth, we also performed comparisons between QTLs of head size traits and growth-related traits. Candidate genes underlying head size traits were identified surrounding the significant SNPs, including parvalbumin, srpk2, fsrp5, igf1 , igf3, grb10, igf1r, notch2, sfrp2. Many of these genes have been identified with potential functions on bone formation and growth. Igf1 was a putative gene associated with both head size and body growth in Yellow River carp. The teleost-specific igf3 was a candidate head size related gene, related to both HL and HBR. Our study also indicated the importance of lgf signaling pathway for both growth and head size determination in common carp, which could be potentially used in future selective breeding in common carp as well as other species.