Friday, August 23, 2013

THE "CHELOID FACTOR" AT THE CELLULAR MEMBRANE!

We tend to be excited about intracellular pathways as they travel through the Cytosol and affect epigenetic and nuclear phenomena. And our excitement has been justified since we have been able to affect cellular life by targeting various pathway molecules. But one should stress a particular event occurring at the membrane that mimics "wound phenomena". Aside for providing a physical boundary of the cell, the membrane is one of the most important "organs" of the cell. It is in itself a very chemically vibrant living "cellular tissue ". When you start reading about the cell they tell you about the layers of proteins and lipids that make up the cellular membranes. But this picture is far from the truth, the membrane is like the wall of a brick house. With each brick different from the next. Some of these bricks are called Integrins (I guess because they are an integral part of the membrane). Some of these bricks have a Cyclin, some have a growth factor! In fact, the membrane here serves as a reserve of these molecules. Some bricks can be divided in 2 portions. One portion that can "FLIP" inside when needed (This portion contains the cyclin, for example) and one portion that can "FLOP" outside (this portion contains a Metalloprotease). (see my post on FLIPPASE and FLOPPASE) The point is that once the brick is used there remains a hole with sharp edges. These edges are called "FOCAL ADHESION Molecules" (KINASES) in a cell and are governed by the PTK2 gene! (and of course PYK2)

PTK2:

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Protein tyrosine kinase 2

PDB rendering of the C-terminal FAT domain based on 1k04^[1].

Available structures

PDB

Ortholog search: PDBe, RCSB

[show]List of PDB id codes

Identifiers

Symbols

PTK2; FADK; FAK; FAK1; FRNK; PPP1R71; p125FAK; pp125FAK

External IDs

OMIM: 600758 MGI: 95481 HomoloGene: 7314 ChEMBL: 2695 GeneCards: PTK2 Gene

EC number

2.7.10.2

[show]Gene Ontology

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 8:
141.67 – 142.01 Mb

Chr 15:
73.21 – 73.42 Mb

PubMed search

[1]

[2]

PTK2 protein tyrosine kinase 2 (PTK2), also known as Focal Adhesion Kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene.^[2] PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around).^[3] It has been shown that when FAK was blocked, breast cancer cells became less metastastic due to decreased mobility.^{[4](Wikepedia}
^{=============================================================================}

^{AND THEY ARE PLENTY TALKED ABOUT!}
^{=============================================================== I.E....}

"Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves specific interactions of p85 alpha with actin filaments and focal adhesion kinase(JCB)"

The point is that at the membrane healing should occur after the "integrin" has been plucked off, but failure to heal may trigger the "cheloid effect". In the cell, this is where the Src gene is, the Wnt (catenins) and the Notch are here, Caspase 3 is present, and death Receptors,etc... (things can get complicated really fast with these guys around! unless of course phosphorylation or other taming mechanisms come to play!)

Focal Adhesion kinases (FAK)

". FAK is typically located at structures known as focal adhesions, these are multi-protein structures that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton. Additional components of focal adhesions include actin, filamin, vinculin, talin, paxillin, tensin^[7] and RSU-1." This is what Taxol and Taxotere find their might! (components of microtubules)

remember tensin is same as PTEN

NIH

" PTEN1

Also known as: BZS; DEC; CWS1; GLM2; MHAM; TEP1; MMAC1; PTEN1; 10q23del
Summary: This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. [provided by RefSeq, Jul 2008]"

Coalition for the Reversal of Breast Cancer Mortality in African American Women