Loading...
Please wait, while we are loading the content...
Similar Documents
Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B enhance insulin-receptor autophosphorylation, extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent signalling.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ahmed, Zamal Pillay, Tahir S. |
| Copyright Year | 2003 |
| Abstract | Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B are adapter proteins and substrates that interact with the activation loop of the insulin-receptor (IR) kinase. These proteins are homologous and share substantial sequence similarity. We previously showed [Ahmed, Smith and Pillay, FEBS Lett. 475, 31-34], for the first time, that insulin-stimulated phosphorylation of APS led to interaction with c-Cbl in 3T3-L1 adipocytes and in transfected Chinese-hamster ovary (CHO) cells. In the present study, we find that insulin stimulates the membrane translocation and phosphorylation of APS to a much greater extent than SH2-B, despite the structural similarity of these proteins. Expression of APS or SH2-B delays IR tyrosine and IR substrate (IRS) dephosphorylation. This enhancement of signalling is also observed downsteam of the receptor. In control cells that lack APS, following insulin stimulation, extracellular-signal-regulated kinase (ERK) and Akt kinase reach maximal activation and then decline to basal levels by 60 min. In contrast, in APS- and SH2-B-expressing cells, ERK and Akt kinase activation remains at peak levels at 60 min. These effects may occur because these proteins either stabilize the active conformation or prevent dephosphorylation of the IR. We therefore conclude that, despite the ability to couple to c-Cbl, APS functions as a positive regulator of IR signalling and, although SH2-B is a poor substrate for the IR, its association with the IR allows it to regulate pathways downstream of the receptor independently of its phosphorylation. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.biochemj.org/content/ppbiochemj/371/2/405.full.pdf |
| PubMed reference number | 12521378v1 |
| Volume Number | 371 |
| Part | 2 |
| Journal | The Biochemical journal |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adipocytes CBL gene Homologous Gene Memory impairment Ovary Phosphatidylinositols Pierre Robin Syndrome Pleckstrin Homology Domains Protein dephosphorylation Proto-Oncogene Proteins c-akt SH2B1 wt Allele Tissue membrane Tyrosine biological signaling ovarian neoplasm v-src protein |
| Content Type | Text |
| Resource Type | Article |
