Abstract
The signaling outputs of Receptor Tyrosine Kinases, G-protein coupled receptors and integrins converge to mediate key cell process such as cell adhesion, cell migration, cell invasion and cell proliferation. Once activated by their ligands, these cell surface proteins recruit and direct a diverse range of proteins to disseminate the appropriate response downstream of the specific environmental cues. One of the key groups of proteins required to regulate these activities is the family of serine/threonine intracellular kinases called Protein Kinase Cs. The activity and subcellular location of PKCs are mediated by a series of tightly regulated events and is dependent on several posttranslational modifications and the availability of second messengers. Protein Kinase Cs exhibit both pro- and anti-tumorigenic effects making them an interesting target for anti-cancer treatment.
Highlights
The composition and organization of the extra-cellular matrix (ECM) regulates cell behaviour and tissue morphogenesis
It is thought that these isozymes may be functioning to regulate c-Met receptor signalling as PKCδ and PKCε mediated phosphorylation at Thr 985 is promoted by HGF itself and rapidly removed by protein phosphatase 2 (PP2A) [88]
The role Receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCR) and integrins play in activating Protein Kinase Cs (PKC) is well characterised and is a key feature of cell proliferation and oncogenic signalling
Summary
The composition and organization of the extra-cellular matrix (ECM) regulates cell behaviour and tissue morphogenesis. An important function of activated cell surface receptors is the recruitment of intracellular kinases [5,15] This recruitment leads to a cascade of downstream signalling and has a major influence on cell characteristics such as cell adhesion, proliferation, migration and invasion [16,17]. A key subgroup of these intracellular kinases are Protein Kinase Cs (PKC), a family of serine/threonine kinases which play key roles in several signalling pathways [29,30,31,32] This group of proteins are expressed in many different tissue types and have a diverse range of biological functions [33,34]. PKCs have been shown to interact with several structural, mechanical and regulatory proteins that are central to the establishment, maintenance and disassembly of focal adhesions (reviewed in [35])
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