About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

After the past three days of blogging focal adhesion kinase (FAK), each focusing on an important regulator of cell adhesion dynamics and cell motility, I’m going to turn my attention to phosphatidyl inositol-3 kinase (PI3K). PI3K has a regulatory subunit (p85), and a catalytic subunit (p110) capable of catalyzing the phosphorylation of the D3 position of the inositol ring of a class of lipid components of the cell membrane. In the inactive state, p85 binds to p110, blocking its activity; but when the Src homology 2 (SH2) domain of p85 finds a phosphotyrosine-containing sequence in another protein that it likes, it dissociates from p110, which is then active.

Among the phosphotyrosine-containing activators of PI3K are FAK (through integrin receptors) and growth factor receptors (or receptor tyrosine kinases, RTK’s). In a recent study, Teet Velling and colleagues in Sweden sought to distinguish between FAK and RTK mechanisms of PI3K activation in EGFR and ?1 integrins utilize different signaling pathways to activate Akt. (more…)

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

In keeping with this week’s trend of just science blogging on FAK, let’s take a look at another critical protein-protein interaction – this time with the scaffolding protein Paxillin. Specifically, how do FAK and Paxillin interact and why?

Conveniently, there’s a recent paper by Danielle Scheswohl et al., from the Schaller lab: Multiple paxillin binding sites regulate FAK function. The motivation to the paper can be found in the abstract: “Recent structural analyses have revealed two paxillin-binding sites in the [focal adhesion targeting, or FAT] domain of FAK. To define the role of paxillin binding to each site on FAK, point mutations have been engineered to specifically disrupt paxillin binding to each docking site on the FAT domain of FAK individually or in combination.” The paxillin binding sites are at the interface of ?-helices 1/4 and the interface of ?-helices 2/3 within the FAT domain (4 helices total). Paxillin is a scaffolding protein containing multiple domains that mediate protein-protein interactions, including five N-terminal LD motifs, four C-terminal LIM domains, and SH2 and SH3 domain binding sites. The second (LD2) and fourth LD motifs (LD4) of paxillin have been identified as FAK-binding sites and each of these sites binds to FAK with similar affinity. (more…)

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

Yesterday, I ended a post about FAK, Pyk2 and regulation of RhoA activity by asking “So, what about Rac regulation by [FAK] and Pyk2?”

Today, let’s discuss a paper relating FAK/Pyk2 function studies on Rac1: Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. Katherine Owen, et al., focus on how “Primary bone marrow macrophages isolated from mice in which FAK is conditionally deleted from cells of the myeloid lineage exhibited elevated protrusive activity, altered adhesion dynamics, impaired chemotaxis, elevated basal Rac1 activity, and a marked inability to form stable lamellipodia necessary for directional locomotion.” (more…)

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

Focal adhesion kinase is an important signaling molecule in integrin-mediated cell signaling and cell adhesion. In FAK genetic knockout (FAK-null) cells, its closely homologous relative proline-rich kinase (Pyk2) is upregulated in FAK-null fibroblasts to partially compensate, but the mechanisms of Pyk2 upregulation and compensation remain undefined¹. A recent study by Yangmi Lim, David Schlaepfer, and colleagues takes a step towards elucidating the latter, by demonstrating both FAK and Pyk2 signaling through a RhoA guanine nucleotide exchange factor (GEF)².
(more…)

About the author

Nick Oswald

Nick is a molecular biologist-turned-publisher. After a PhD in Developmental Biology and an eclectic seven years in biotech he is now Editorial Manager of Neuroendocrinology and the founder and Editor-In-Chief of Bitesize Bio. You are welcome to connect with Nick on LinkedIn

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

You know about adenine, thymine, guanine, cytosine. Now get used to SICS and MMO2.

In this JACS article published this month, researchers at the Scripps Institute reported the identification of these two artificial bases. They are efficiently incorporated during in vivo DNA synthesis by the Klenow fragment of E.coli DNA polymerase and pair together with high fidelity.

At the moment the applications for these new bases are are limited mainly to providing new building blocks for the in vivo synthesis of DNA-based nanostructures. However, work is ongoing to incorporate them into living cells and make them code for specific amino acids. Although it is far from clear whether this can be done, if achieved it will lead to some new, very powerful tools for protein engineering.

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

One of the several popular views regarding the origin of life stems from thermodynamics. Harold Morowitz refers to it as “Metabolism recapitulates biogenesis”.

In PLoS Biology there’s an interesting essay that was submitted posthumously by the chemist Leslie Orgel on this subject – The Implausibility of Metabolic Cycles on the Prebiotic Earth. Orgel takes a hearty dose of skepticism to contemporary hypotheses presented by W?¤chtersh?¤user and Morowitz^3,4, including the reverse citric acid cycle in particular. For clarification: the reverse citric acid cycle has been proposed to have operated nonenzymatically, not only fixing carbon but (in a chaotic soup-like mixture of inorganic catalysts) also producing metabolic intermediates for many of the amino acids, nucleotides, etc., required for the later RNA world.
(more…)

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

Form follows physics in the fly eye, say Sascha Hilgenfeldt, Sinem Erisken, and Richard Carthew

Simple forces, complex shapes: While most biological features appear complex in their geometries and varieties of components, appearances can be deceiving. That finding is supported by a recent modeling study by Hilgenfeldt, et al., looking at the arrangement of cone cells in the Drosophilia eye. They found that cell elasticity and adhesion strength alone can explain the cell arrangement, into the image shown (source: Hilgenfeldt/NAS).
(more…)

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

Here’s a comment on work published about 6 months ago that was relevant to me, given my graduate studies on FAK with Jun-Lin Guan. The relations between protein structures and evolution are quite interesting indeed.

As more structures are being solved for multimodular signaling proteins, the regulatory kinetics (on, off, and everything in between) is coming into greater clarity. For instance, the recently solved structural basis for allosteric autoinhibition of focal adhesion kinase (FAK), along with the ZAP-70 tyrosine kinase, and the protypical tyrosine kinase Src.

As with all comparisons within protein families involving crystallography, the stories that come out of the research relate to the structural plasticity of the crystals themselves, and how homologous proteins (of both orthologous and paralogous flavors) find such diverse regulatory mechanisms. For kinases in general, we have the basic catalytic unit, which evolved long before the advent of eukaryotic cells, and diverged into tyrosine, serine/threonine, lipid, and atypical phosphorylating enzymes by many gene duplication and exaption events.

For individual kinase subfamilies, innovative mechanisms¹ for modulating catalytic activity abound. Every part of a protein not absolutely required (or conserved) for catalytic activity becomes a candidate enhancing mutation, enabling both complexity and control. (more…)

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

Two blog posts recently collided for me. First, in a blog discussion on Macroevolution vs. Microevolution, Allen MacNeill clarified some issues for me (thanks to TUIBG for bringing it back up):

Add the newly emerging fields of evo-devo and epigenesis to the foregoing, and it is increasingly clear that macroevolution (i.e. cladogenesis) follows different rules than microevolution (i.e. anagenesis), and that these differences are most noticeable in the fossil record cited by Eldredge and Gould as the basis for their theory of punctuated equilibrium. In particular, the basic program that energized the �modern synthesis� – that is, the reduction of all significant evolutionary mechanisms to a series of linked mathematical models, based on grossly simplified reductions of complex biology to quasi-Mendelian point-like �particles of inheritance� (changes in which drive the variation and divergence of phenotypes) – is impossible to apply in any coherent way to macroevolution. The �modern synthesis� was essentially a �Newtonian� program, whose proponents assumed that the underlying law-like processes (i.e. microevoluiton) are (like physics) both ahistorical and universal. However, it is now becoming clear that the emerging science of macroevolution is both irreversibly historically contingent (and therefore not reducible to mathematical formalisms) and driven by fundamentally different processes than those underlying most of microevolution.

Rich Lawler’s comment at Gene Expression counter-balances that comment with an item on Formalization and Process:

It’s interesting to note that a few of the most insightful observations about the evolutionary process were first promulgated verbally, then later proven mathematically (unlike H-W equilibrium). These include runaway sexual selection (first adumbrated by Fisher, then shown mathematically possible by Lande and Kirkpatrick), the handicap principle (first adumbrated by Zahavi, then–finally–shown to be mathematically possible by Grafen), and, of course, natural selection (first adumbrated by what’s-his-face, then formalized by Wright, Fisher, and later Price, among others). And of course, all of these topics were debated back-n-forth until the math made them more clear.

(more…)

About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

To enable tagging you will need to register on Bitesize Bio. We're sorry for the inconvenience, but it's free, only takes a few seconds, and it will enable you to view our seminars for free, ask questions from the professional community, and take part in the lively community of Bitesize Bio

Amid the political controversy and obstructions to conducting stem cell research, scientists this year managed to turn lead into gold… Genetically manipulating fibroblasts to become ESC(embryonic stem cell)-like sort of sounds like alchemy in a way, doesn’t it? The product of these papers, inducible pluripotent stem (iPS) cells, were created by transfecting four factors into fibroblasts, Oct3/4, Sox2, c-Myc, and Klf4, and they found that the epigenetic, morphological, and proliferative characteristics resembled those of embryonic stem cells. (more…)