CD36Mediated Intracellular Signaling

CD36 is known to mediate intracellular signaling. The molecule is physically associated with Src-family kinases in membrane invaginations known as caveolae that are enriched in a variety of signal transduction molecules. Cave-olae serve as a subcompartment of the plasma membrane where clustering of signaling proteins may result in more rapid cross talk and/or promote efficiency of signal transmission. The binding of one of the natural ligand TSP-1 to CD36 on dermal microvascular endothelial cells sequentially activates the Src-family kinase Fyn, caspase-3-like proteases, and the p38 MAPK pathway. As well, a CD36-mediated signaling cascade involving the Src-family kinases

MCvar-1 |DBL1n)^CÏDRÎ~^(DBL2^ CIDR2 ^DBL3^[dBL4i: J |

- CD36 minimal binding region

Figure 3 Structural domains of PfEMP1 from the parasite clone MCvarl for which the minimal CD36 binding site (179 amino acids) has been mapped to the CIDR region 1. DBL, Duffy binding-like; CIDR, cysteine-rich interdomain.

Lyn and Fyn is responsible for the inflammatory effects of fibrillar b-amyloid in mouse peritoneal macrophages and microglial cells. Several lines of evidence in the literature suggest that IRBC adhesion might also induce intracellular signaling. IRBC adhesion to CD36 on human monocytes induces a respiratory burst, and cross-linking of CD36 on monocytes by OKM5 activates both the ERK 1/2 and p38 MAP kinase pathways. IRBCs have also been shown to modulate the maturation of dendritic cells through an interaction with cell surface CD36.

An additional feature of platelet CD36 is that it is con-stitutively phosphorylated on its ectodomain on residue Thr92 that results in a low-affinity receptor for TSP-1. Initial CD36-TSP-1 interaction induces platelet degranulation with release of acid phosphatases capable of dephosphory-lating the ectodomain of CD36, resulting in a high-affinity receptor for TSP-1. Although the phosphorylated isoform of CD36 have not been identified on endothelium, the PKC-dependent targeting sequence RGPYTYRVRFLA for Thr92 phosphorylation is conserved in the endothelial protein. The close proximity of CD36, dually acylated Src-family kinases, and a glycosylphosphatidylinositol (GPI)-anchored alkaline phosphatase in caveolae suggests that a change in the phosphorylation state of endothelial CD36 might also occur upon ligand binding and intracellular signal activation.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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