Class IA phosphoinositide 3-kinase modulates basal lymphocyte motility in the lymph node.
نویسندگان
چکیده
Recruitment of PI3K to the cell membrane is an indispensable step in normal lymphocyte proliferation and activation. In this study we identify PI3K as an important signaling molecule for maintaining basal T and B lymphocyte motility and homing in the intact lymph node. Pharmacological inhibition of PI3K catalytic isoforms exerted broad effects on basal lymphocyte motility, including changes in homing kinetics, localization of B cells within the lymph node, and reduced cell velocities. Lymphocytes deficient in either or both of the class IA PI3K regulatory subunits p85alpha and p85beta also exhibited reduced velocities, with the magnitude of reduction depending upon both cell type and isoform specificity. B cells deficient in p85alpha exhibited gross morphological abnormalities that were not evident in cells treated with a PI3K inhibitor. Our results show, for the first time, that class IA PI3Ks play an important role in regulating basal lymphocyte motility and that p85alpha regulatory subunit expression is required to maintain B cell morphology in a manner independent of PI3K catalytic function. Moreover, we demonstrate distinct roles for catalytic domain function and class IA PI3K regulatory domain activity in lymphocyte motility, homing, and homeostatic localization of mature resting B cells.
منابع مشابه
Lymphocyte cell motility: the twisting, turning tale of phosphoinositide 3-kinase.
The PI3K (phosphoinositide 3-kinase) family of lipid kinases regulate cell motility in diverse organisms and cell types. In mammals, the main PI3K enzyme activated by chemokine receptor signalling is the class IB isoform, p110gamma. Studies of p110gamma-knockout mice have shown an essential function for this isoform in chemotaxis of neutrophils and macrophages both in vitro and in vivo. However...
متن کاملCCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3–kinase– independent manner
The molecular mechanisms responsible for the sustained basal motility of T cells within lymph nodes (LNs) remain elusive. To study T cell motility in a LN environment, we have developed a new experimental system based on slices of LNs that allows the assessment of T cell trafficking after adoptive transfer or direct addition of T cells to the slice. Using this experimental system, we show that ...
متن کاملRole of class IA phosphoinositide 3-kinase in B lymphocyte development and functions.
PI3K (phosphoinositide 3-kinase) family members control a variety of cellular responses, such as cell growth, survival, cytoskeletal remodelling and the trafficking of intracellular organelles, in many cell types, including lymphocytes. It has been difficult to evaluate the roles of distinct PI3Ks in immune responses, because specific inhibitors for each PI3K are lacking and most stimuli activa...
متن کاملCell, Tumor, and Stem Cell Biology Differential Enhancement of Breast Cancer Cell Motility and Metastasis by Helical and Kinase Domain Mutations of Class IA Phosphoinositide 3-Kinase
Class IA (p85/p110) phosphoinositide 3-kinases play a major role in regulating cell growth, survival, and motility. Activating mutations in the p110α isoform of the class IA catalytic subunit (PIK3CA) are commonly found in human cancers. These mutations lead to increased proliferation and transformation in cultured cells, but their effects on cell motility and tumor metastasis have not been eva...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 179 4 شماره
صفحات -
تاریخ انتشار 2007