Red Blood Cell Surface Receptor Expression of BCAM/Lu is Regulated by Protein Kinase A Activity

Author(s):  
J. L. Maciaszek ◽  
B. Andemariam ◽  
G. Lykotrafitis

Irregular sickle red blood cells (RBCs) can contribute to the pathogenesis of vasoocclusion and other complications of sickle cell disease (SCD) via abnormal adherence to the vascular endothelium. It has previously been demonstrated that epinephrine enhances SCD RBC adhesion by activating the BCAM/Lu and ICAM-4 surface receptors [1–2]. Epinephrine acts on the RBC β2-adrenergic receptor, thereby activating Gas proteins that stimulate adenylyl cyclase (AC). This enzyme catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), leading to protein kinase A (PKA) activation, an intermediate step in the upregulation of BCAM/Lu and ICAM-4 mediated adhesion. The interaction of BCAM/Lu with the α5 chain of laminin may contribute to vaso-occlusive events in SCD due to overexpression of BCAM on SCD RBCs.

2007 ◽  
Vol 176 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Jianzhong Han ◽  
Liang Han ◽  
Priyanka Tiwari ◽  
Zhexing Wen ◽  
James Q. Zheng

The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role in axonal growth and guidance, but its downstream mechanisms remain elusive. In this study, we report that type II protein kinase A (PKA) is highly enriched in growth cone filopodia, and this spatial localization enables the coupling of cAMP signaling to its specific effectors to regulate guidance responses. Disrupting the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction and prevents the switching of repulsive responses to attraction by elevated cAMP. Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone attraction. Finally, we find that I-1 and PP1 mediate growth cone repulsion induced by myelin-associated glycoprotein. These findings demonstrate that the spatial localization of type II PKA to growth cone filopodia plays an important role in the regulation of growth cone motility and guidance by cAMP.


2020 ◽  
Vol 11 ◽  
Author(s):  
Chong Liu ◽  
Ping Ke ◽  
Jingjing Zhang ◽  
Xiaoying Zhang ◽  
Xiongwen Chen

The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival. Protein kinase A (PKA), whose activation is triggered by cyclic adenosine monophosphate (cAMP), is widely distributed in various systems and tissues throughout the body and highly related to pathogenesis and progression of various kinds of diseases. The inhibition of PKA activation is essential for the study of PKA functions. Protein kinase inhibitor peptide (PKI) is a potent, heat-stable, and specific PKA inhibitor. It has been demonstrated that PKI can block PKA-mediated phosphorylase activation. Since then, researchers have a lot of knowledge about PKI. PKI is considered to be the most effective and specific method to inhibit PKA and is widely used in related research. In this review, we will first introduce the knowledge on the activation of PKA and mechanisms related on the inhibitory effects of PKI on PKA. Then, we will compare PKI-mediated PKA inhibition vs. several popular methods of PKA inhibition.


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