SSTR4 Membrane Protein Introduction

Introduction of SSTR4

SSTR4 (Somatostatin Receptor 4) is a protein that in human is encoded by the SSTR4 gene. And it belongs to the G-protein coupled receptor superfamily (GPCR). SSTR4 has extracellular N-linked glycosylation sites (N-termini, second extracellular loop), a disulphide bridge (between the first two extracellular loops) and many intracellular phosphorylation sites (second and third intracellular loops and C-termini). Its biological effects of somatostatins are mediated by a family of G-protein coupled somatostatin receptors that are expressed in a tissue-specific manner. SSTR4 is functionally coupled to adenylyl cyclase.

Function of SSTR4 Membrane Protein

Somatostatins are peptide hormones that regulate diverse cellular functions such as neurotransmission, cell proliferation, and endocrine signaling as well as inhibiting the release of many hormones and other secretory proteins. The activity of SSTR4 is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. The study shows SSTR4 is a member of the superfamily of receptors which have seven transmembrane segments and is expressed in highest levels in fetal and adult brain and lung. Receptors SSTR1, SSTR2 and SSTR4, located on neurones in the hypothalamus, were thought to mediate opposing effects via different signal transduction mechanisms: SST1 and SST4 enhancing the response to glutamate.

Fig.1 Structure of SSTR4 membrane protein.

Application of SSTR4 Membrane Protein in Literature

1. Song K.B., et al. Prognostic Value of Somatostatin Receptor Subtypes in Pancreatic Neuroendocrine Tumors. Pancreas. 2016, 45(2):187-92. PubMed ID: 26474434
   
   

   This article determines the expression of the SSTR subtypes via immunohistochemistry analyses and assesses the correlation between SSTR subtype expression and prognosis. And data showed that the distribution of somatostatin receptor (SSTR) subtypes among the 199 pancreatic neuroendocrine tumors (PNETs) was: SSTR2 (54.8%), SSTR1 (53.3%), SSTR4 (51.8%), SSTR5 (33.7%), and SSTR3 (28.6%).

2. Grosser C., et al. Methylation analysis of SST and SSTR4 promoters in the neocortex of Alzheimer's disease patients. Neuroscience letters. 2014, 566:241-6. PubMed ID: 24602981.
   
   

   This article found that deregulated somatostatin signaling in the AD cortices studied cannot be explained by hypermethylation of the SST or SSTR4 promoter CpG islands.

3. Yamamoto J., et al. Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma. British journal of cancer. 2014,110(9):2232-45. PubMed ID: 24743707.
   
   

   Author of this group identifies that cytostatic effects in MPM are mediated by SSTR4, being inhibited by the interaction of CD26 molecules. They think combination therapy with humanized anti-CD26 mAb and SSTR4 agonist may therefore potentiate anti-tumour effect on MPM.

4. Nakayama Y., et al. Profiling of somatostatin receptor subtype expression by quantitative PCR and correlation with clinicopathological features in pancreatic endocrine tumors. Pancreas. 2010,39(8):1147-54. PubMed ID: 20717067.
   
   

   This article explores the correlation between the SSTR subtype messenger RNA (mRNA) expression and clinicopathological features of PET. And the data also shows the mRNA levels of SSTR1, SSTR2, SSTR3, and SSTR5 were high in PET compared with AC, whereas the expression of SSTR4 was low in PET and AC.

5. Casarini A.P., et al. Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment. Pituitary. 2009,12(4):297-303. PubMed ID: 19330452.
   
   

   This article analyzes 39 somatotrophinomas patients treated with somatostain analogs, and found the most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively.

SSTR4 Preparation Options

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