Caveolin1 Tyrosine-14 Phosphorylation: Role in Cellular Responsiveness to Mechanical Cues
JOURNAL OF MEMBRANE BIOLOGY
Authors: Buwa, Natasha; Mazumdar, Debasmita; Balasubramanian, Nagaraj
Abstract
The plasma membrane is a dynamic lipid bilayer that engages with the extracellular microenvironment and intracellular cytoskeleton. Caveolae are distinct plasma membrane invaginations lined by integral membrane proteins Caveolin1, 2, and 3. Caveolae formation and stability is further supported by additional proteins including Cavin1, EHD2, Pacsin2 and ROR1. The lipid composition of caveolar membranes, rich in cholesterol and phosphatidylserine, actively contributes to caveolae formation and function. Post-translational modifications of Cav1, including its phosphorylation of the tyrosine-14 residue (pY14Cav1) are vital to its function in and out of caveolae. Cells that experience significant mechanical stress are seen to have abundant caveolae. They play a vital role in regulating cellular signaling and endocytosis, which could further affect the abundance and distribution of caveolae at the PM, contributing to sensing and/or buffering mechanical stress. Changes in membrane tension in cells responding to multiple mechanical stimuli affects the organization and function of caveolae. These mechanical cues regulate pY14Cav1 levels and function in caveolae and focal adhesions. This review, along with looking at the mechanosensitive nature of caveolae, focuses on the role of pY14Cav1 in regulating cellular mechanotransduction. [GRAPHICS] .
Periosteal Reaction Possibly Induced by Pazopanib: A Case Report and Literature Review
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
Authors: Hosokawa, Takahiro; Hara, Tomoko; Arakawa, Yuki; Oguma, Eiji; Yamada, Yoshitake
Abstract
Background: Although complications associated with pazopanib, a multitarget tyrosine kinase inhibitor, are known, periosteal reaction as a side effect has never been reported. Observation: We present a case involving a male pediatric patient with desmoid tumors treated for 6 months with pazopanib who presented with pain and periosteal reaction in the ilium and scapula. Three months after termination of pazopanib therapy, the periosteal reaction in the scapula resolved and that in the ilium improved. Conclusion: Children receiving pazopanib presenting with focal pain should be examined for the periosteal reaction; this knowledge may facilitate correct diagnosis of symptoms as a drug-associated finding.