title: Mechanisms that underlie the internalization and extracellular signal regulated kinase 1/2 activation by PKR2 receptor.
abstract: Prokineticins (PKs) are a pair of signal factors involved in many physiological processes by binding to two closely related G-protein-coupled receptors (GPCRs), PKR1 and PKR2. We recently demonstrated that PKR2 undergoes rapid ligand-induced endocytosis, and PKR2 recycles back to the plasma membrane after the removal of ligand. However, little is known about the molecular mechanisms underlying the PKR2 endocytosis. Here, we studied the involvement of GPCR kinase 2 (GRK2), β-arrestins, clathrin and protein kinase C (PKC) in the PKR2 endocytosis. Our results indicated that PK2-induced PKR2 endocytosis is GRK2- and clathrin-dependent, but β-arrestin-independent. PKC activation also induced PKR2 endocytosis; however, PKC activation is not necessary for the PK2-induced PKR2 endocytosis. PK2 stimulation induced a transient activation of extracellular signal regulated kinase 1/2 (ERK1/2) on PKR2 expressing cells. The internalization and PKC activation are not required for the PK2-induced ERK1/2 activation. Our results indicated that PK2-induced ERK1/2 activation may involve the released βγ subunits of G-protein, phospholipase C β and MEK activation.
authors: The Second Xiangya Hospital, State Key Laboratory of Medical Genetics, Changsha, Hunan, China.
authors: Wenqing
authors: W
authors: Yin
authors: The Second Xiangya Hospital, State Key Laboratory of Medical Genetics, Changsha, Hunan, China.
authors: Huadie
authors: H
authors: Liu
authors: The Second Xiangya Hospital, State Key Laboratory of Medical Genetics, Changsha, Hunan, China.
authors: Zhen
authors: Z
authors: Peng
authors: The Second Xiangya Hospital, State Key Laboratory of Medical Genetics, Changsha, Hunan, China.
authors: Danna
authors: D
authors: Chen
authors: School of Life Sciences, Central South University, Changsha, Hunan, China. Electronic address: jlee@mail.csu.edu.cn.
authors: Jie
authors: J
authors: Li
authors: The Second Xiangya Hospital, State Key Laboratory of Medical Genetics, Changsha, Hunan, China; School of Life Sciences, Central South University, Changsha, Hunan, China. Electronic address: lijiada@sklmg.edu.cn.
authors: Jia-Da
authors: JD
authors: Li
mesh_terms: D019390:Arrestins / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000494:pharmacology; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D000071557:beta-Arrestins; D011493:Protein Kinase C; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013110:Sphingosine
keywords: ERK1/2; Endocytosis; PKR2; Prokineticin