Posts Tagged ‘#TUBiol3373’

Poll for Students of #TUBiol3373: Cell Signaling and Motility class

As your instructor of your Cell Signaling and Motility class, I am  conducting this poll to try to understand how useful the supplemental information of this website ( and online journal was toward your needs in the course Cell Signaling and Motility.  In addition, I would like to determine the ease of use and to find needed information from this site in order for you to complete projects as well as find extra study materials.  In addition, I am trying to understand if students might use this for other topics as well as the utility of the information in this site/journal for continued learning.


All answers are completely confidential and participation in this poll is voluntary, and no other information is collected.


Stephen J. Williams, PhD

Do you find using an open access, curated information platform like this site more useful than using multiple sources to find useful extra study/presentation material?

Do you find using a web based platform such as a site like this an easier communication platform for posting lecture notes/added information than a platform like Canvas?

Thank you for your participation in this poll.



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Lesson 10 on Cancer, Oncogenes, and Aberrant Cell Signal Termination in Disease for #TUBiol3373

Curator: Stephen J. Williams

Please click on the following file to get the Powerpoint Presentation for this lecture

cell signaling 10 lesson_SJW 2019

There is a good reference to read on The Hallmarks of Cancer published first in 2000 and then updated with 2 new hallmarks in 2011 (namely the ability of cancer cells to reprogram their metabolism and 2. the ability of cancer cells to evade the immune system)

a link to the PDF is given here:



Please also go to other articles on this site which are relevant to this lecture.  You can use the search box in the upper right hand corner of the Home Page or these are few links you might find interesting

Development of Chemoresistance to Targeted Therapies: Alterations of Cell Signaling & the Kinome

Proteomics, Metabolomics, Signaling Pathways, and Cell Regulation: a Compilation of Articles in the Journal

Feeling the Heat – the Link between Inflammation and Cancer

Lesson 4 Cell Signaling And Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373

Immunotherapy Resistance Rears Its Ugly Head: PD-1 Resistant Metastatic Melanoma and More

Novel Mechanisms of Resistance to Novel Agents


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Lesson 8 Cell Signaling and Motility: Lesson and Supplemental Information on Cell Junctions and ECM: #TUBiol3373

Curator: Stephen J. Williams, Ph.D.

Please click on the following link for the PowerPoint Presentation for Lecture 8 on Cell Junctions and the  Extracellular Matrix: (this is same lesson from 2018 so don’t worry that file says 2018)

cell signaling 8 lesson 2018


Some other reading on this lesson on this Open Access Journal Include:

On Cell Junctions:

Translational Research on the Mechanism of Water and Electrolyte Movements into the Cell     

(pay particular attention to article by Fischbarg on importance of tight junctions for proper water and electrolyte movement)

The Role of Tight Junction Proteins in Water and Electrolyte Transport

(pay attention to article of role of tight junction in kidney in the Loop of Henle and the collecting tubule)

EpCAM [7.4]

(a tight junction protein)

Signaling and Signaling Pathways

(for this lesson pay attention to the part that shows how Receptor Tyrosine Kinase activation (RTK) can lead to signaling to an integrin and also how the thrombin receptor leads to cellular signals both to GPCR (G-protein coupled receptors like the thrombin receptor, the ADP receptor; but also the signaling cascades that lead to integrin activation of integrins leading to adhesion to insoluble fibrin mesh of the newly formed clot and subsequent adhesion of platelets, forming the platelet plug during thrombosis.)

On the Extracellular Matrix

Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function Post MI

Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel


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Lesson 5 Cell Signaling And Motility: Cytoskeleton & Actin: Curations and Articles of reference as supplemental information: #TUBiol3373

Curator: Stephen J. Williams, Ph.D.

Cell motility or migration is an essential cellular process for a variety of biological events. In embryonic development, cells migrate to appropriate locations for the morphogenesis of tissues and organs. Cells need to migrate to heal the wound in repairing damaged tissue. Vascular endothelial cells (ECs) migrate to form new capillaries during angiogenesis. White blood cells migrate to the sites of inflammation to kill bacteria. Cancer cell metastasis involves their migration through the blood vessel wall to invade surrounding tissues.

Please Click on the Following Powerpoint Presentation for Lesson 4 on the Cytoskeleton, Actin, and Filaments


cell signaling 5 lesson

This post will be updated with further information when we get into Lesson 6 and complete our discussion on the Cytoskeleton

Please see the following articles on Actin and the Cytoskeleton in Cellular Signaling

Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility

This article, constitutes a broad, but not complete review of the emerging discoveries of the critical role of calcium signaling on cell motility and, by extension, embryonic development, cancer metastasis, changes in vascular compliance at the junction between the endothelium and the underlying interstitial layer.  The effect of calcium signaling on the heart in arrhtmogenesis and heart failure will be a third in this series, while the binding of calcium to troponin C in the synchronous contraction of the myocardium had been discussed by Dr. Lev-Ari in Part I.

Universal MOTIFs essential to skeletal muscle, smooth muscle, cardiac syncytial muscle, endothelium, neovascularization, atherosclerosis and hypertension, cell division, embryogenesis, and cancer metastasis. The discussion will be presented in several parts:
1.  Biochemical and signaling cascades in cell motility
2.  Extracellular matrix and cell-ECM adhesions
3.  Actin dynamics in cell-cell adhesion
4.  Effect of intracellular Ca++ action on cell motility
5.  Regulation of the cytoskeleton
6.  Role of thymosin in actin-sequestration
7.  T-lymphocyte signaling and the actin cytoskeleton


Identification of Biomarkers that are Related to the Actin Cytoskeleton

In this article the Dr. Larry Bernstein covers two types of biomarker on the function of actin in cytoskeleton mobility in situ.

  • First, is an application in developing the actin or other component, for a biotarget and then, to be able to follow it as

(a) a biomarker either for diagnosis, or

(b) for the potential treatment prediction of disease free survival.

  • Second, is mostly in the context of MI, for which there is an abundance of work to reference, and a substantial body of knowledge about

(a) treatment and long term effects of diet, exercise, and

(b) underlying effects of therapeutic drugs.

Microtubule-Associated Protein Assembled on Polymerized Microtubules

(This article has a great 3D visualization of a microtuble structure as well as description of genetic diseases which result from mutations in tubulin and effects on intracellular trafficking of proteins.

A latticework of tiny tubes called microtubules gives your cells their shape and also acts like a railroad track that essential proteins travel on. But if there is a glitch in the connection between train and track, diseases can occur. In the November 24, 2015 issue of PNAS, Tatyana Polenova, Ph.D., Professor of Chemistry and Biochemistry, and her team at the University of Delaware (UD), together with John C. Williams, Ph.D., Associate Professor at the Beckman Research Institute of City of Hope in Duarte, California, reveal for the first time — atom by atom — the structure of a protein bound to a microtubule. The protein of focus, CAP-Gly, short for “cytoskeleton-associated protein-glycine-rich domains,” is a component of dynactin, which binds with the motor protein dynein to move cargoes of essential proteins along the microtubule tracks. Mutations in CAP-Gly have been linked to such neurological diseases and disorders as Perry syndrome and distal spinal bulbar muscular dystrophy.


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Lesson 3 Cell Signaling & Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373

Curator: Stephen J. Williams, Ph.D.

Lesson 3 Powerpoint (click link below):

cell signaling and motility 3 finalissima sjw

Four papers to choose from for your February 11 group presentation:

Structural studies of G protein Coupled receptor


G protein as target in neurodegerative disease

fish technique



Today’s lesson 3 explains how extracellular signals are transduced (transmitted) into the cell through receptors to produce an agonist-driven event (effect).  This lesson focused on signal transduction from agonist through G proteins (GTPases), and eventually to the effectors of the signal transduction process.  Agonists such as small molecules like neurotransmitters, hormones, nitric oxide were discussed however later lectures will discuss more in detail the large growth factor signalings which occur through receptor tyrosine kinases and the Ras family of G proteins as well as mechanosignaling through Rho and Rac family of G proteins.

Transducers: The Heterotrimeric G Proteins (GTPases)

An excellent review of heterotrimeric G Proteins found in the brain is given by

Heterotrimeric G Proteins by Eric J Nestler and Ronald S Duman.



from Seven-Transmembrane receptors – Scientific Figure on ResearchGate. Available from: [accessed 4 Feb, 2019] and see references within



See below for the G Protein Cycle









<a href=”″><img src=”; alt=”.3.2: The G protein cycle. In the absence of agonist (A), GPCRs are mainly in the low affinity state (R). After agonist binding, the receptor is activated in the high affinity state (R*), and the agonist-GPCR-G protein complex is formed. GTP replaces GDP in Gα. After that the G protein dissociates into the Gα subunit and the Gβγ heterodimer, which then activate several effector proteins. The built-in GTPase activity of the Gα subunit cleaves the terminal phosphate group of GTP, and the GDP bound Gα subunit reassociates with Gβγ heterodimer. This results in the deactivation of both Gα and Gβγ. The G protein cycle returns to the basal state. RGS, regulator of G protein signalling.”/></a>


From Citation: Review: A. M. Preininger, H. E. Hamm, G protein signaling: Insights from new structures. Sci. STKE2004, re3 (2004)


For a tutorial on G Protein coupled receptors (GPCR) see




cyclic AMP (cAMP) signaling to the effector Protein Kinase A (PKA)


Cyclic AMP is an important second messenger. It forms, as shown, when the membrane enzyme adenylyl cyclase is activated (as indicated, by the alpha subunit of a G protein).


The cyclic AMP then goes on the activate specific proteins. Some ion channels, for example, are gated by cyclic AMP. But an especially important protein activated by cyclic AMP is protein kinase A, which goes on the phosphorylate certain cellular proteins. The scheme below shows how cyclic AMP activates protein kinase A.

Additional information on Nitric Oxide as a Cellular Signal

Nitric oxide is actually a free radical and can react with other free radicals, resulting in a very short half life (only a few seconds) and so in the body is produced locally to its site of action (i.e. in endothelial cells surrounding the vascular smooth muscle, in nerve cells). In the late 1970s, Dr. Robert Furchgott observed that acetylcholine released a substance that produced vascular relaxation, but only when the endothelium was intact. This observation opened this field of research and eventually led to his receiving a Nobel prize. Initially, Furchgott called this substance endothelium-derived relaxing factor (EDRF), but by the mid-1980s he and others identified this substance as being NO.

Nitric oxide is produced from metabolism of endogenous substances like L-arginine, catalyzed by one of three isoforms of nitric oxide synthase (for link to a good article see here) or release from exogenous compounds like drugs used to treat angina pectoris like amyl nitrate or drugs used for hypertension such as sodium nitroprusside.

The following articles are a great reference to the chemistry, and physiological and pathological Roles of Nitric Oxide:

46. The Molecular Biology of Renal Disorders: Nitric Oxide – Part III

Curator and Author: Larry H Bernstein, MD, FACP

47. Nitric Oxide Function in Coagulation – Part II

Curator and Author: Larry H. Bernstein, MD, FCAP

48. Nitric Oxide, Platelets, Endothelium and Hemostasis

Curator and Author: Larry H Bernstein, MD, FACP

49. Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium

Curator and Author: Larry H Bernstein, MD, FACP

50. Nitric Oxide and Immune Responses: Part 1

Curator and Author:  Aviral Vatsa PhD, MBBS

51. Nitric Oxide and Immune Responses: Part 2

Curator and Author:  Aviral Vatsa PhD, MBBS

56. Nitric Oxide and iNOS have Key Roles in Kidney Diseases – Part II

Curator and Author: Larry H Bernstein, MD, FACP

57. New Insights on Nitric Oxide donors – Part IV

Curator and Author: Larry H Bernstein, MD, FACP

59. Nitric Oxide has a ubiquitous role in the regulation of glycolysis -with a concomitant influence on mitochondrial function

Curator and Author: Larry H Bernstein, MD, FACP         a-concomitant-influence-on-mitochondrial-function/

Biochemistry of the Coagulation Cascade and Platelet Aggregation: Nitric Oxide: Platelets, Circulatory Disorders, and Coagulation Effects

Nitric Oxide Function in Coagulation – Part II

Nitric oxide is implicated in many pathologic processes as well.  Nitric oxide post translational modifications have been attributed to nitric oxide’s role in pathology however, although the general mechanism by which nitric oxide exerts its physiological effects is by stimulation of soluble guanylate cyclase to produce cGMP, these post translational modifications can act as a cellular signal as well.  For more information of NO pathologic effects and how NO induced post translational modifications can act as a cellular signal see the following:

Nitric Oxide Covalent Modifications: A Putative Therapeutic Target?

58. Crucial role of Nitric Oxide in Cancer

Curator and Author: Ritu Saxena, Ph.D.

Note:  A more comprehensive ebook on Nitric Oxide and Disease Perspectives is found at

Cardiovascular Diseases, Volume One: Perspectives on Nitric Oxide in Disease Mechanisms

available on Kindle Store @

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Lesson 1 & 2 Cell Signaling & Motility: Lessons, Curations and Articles of reference as supplemental information: #TUBiol3373

Curator: Stephen J. Williams, Ph.D.

UPDATED 2/05/2019

Syllabus for Cell Signaling & Motility for 2019




Monday 5:00 PM – 8:00 PM

Biology Life Sciences, Room 342


Antonio Giordano, M.D., Ph.D.

Office hours: Biology Life Sciences Building, Room 431.

Friday: 12:00 noon – 2:00 PM. By appointment

(Phone: 215-2049520, or email:


BIO 3096, Cell Structure and Function (Minimum Grade of C- | May not be taken concurrently). 


The communication among cells is essential for the regulation of the development of an organism and for the control of its physiology and homeostasis. Aberrant cellular signaling events are often associated with human pathological conditions, such as cancer, neurological disorders, cardiovascular diseases and so on. The full characterization of cell signaling systems may provide useful insights into the pathogenesis of several human maladies.


Molecular Biology of the Cell 6th Edition, Alberts et al. Garland Science. This textbook is available at the Temple Bookstore.


The final grade will be based on the score of four examinations that include both group and individuals assignment. Each exam accounts for 25% of the final grade. There will be no make-up tests during the course. If you have a documented medical excuse and you contact me as soon as possible after the emergency, I will arrange a make-up exam. Complaints regarding the grading will not be considered later than two weeks after the test is returned.


Announcements will be readily posted on Blackboard. It is your responsibility to check Blackboard periodically.

Attendance: Lecture attendance is mandatory. In addition, punctuality is expected.

Disabilities: Students with documented disabilities who need particular accommodation should contact me privately as soon as possible.

Honesty and Civility:

Students must follow the Temple’s Code of Conduct (see This Code of Conduct prohibits: 1. Academic dishonesty and impropriety, including plagiarism and cheating. 2. Interfering or attempting to interfere with or disrupting the conduct of classes or any other activity of the University.”

Academic Rights and Responsibilities:

The policy of the University that regulates Student and Faculty Academic Rights and Responsibilities (Policy # 03.70.02) is available at the following web link:

This policy sets the parameters for freedom to learn and freedom to teach, which constitute the pillars of academia.



This schedule is a general outline, which may be eventually modified. Changes will be announced in advance. Please, always check Blackboard and your email.

Date Topic
Jan 14 Introduction (course overview  and discussion of syllabus). General concepts: Eukaryotic and prokaryotic cell; DNA, RNA  and proteins: Protein synthesis
Jan 21 Martin Luther King, Jr. Day (no classes held)
Jan 28 DNA analysis, RNA analysis; Proteins analysis; Microscopy.
Feb 4 Signaling: general concepts; Introduction to G-proteins; signaling via G-proteins (1)
Feb 11 Exam 1: In class presentation (group assignment)
Feb 18 Signaling via G-proteins (2); tyrosine kinase receptors signaling; Ras-MAPK pathway.
Feb 25 Exam 2: In class presentation (group assignment)
March 4- 10 Spring break
Mar 11


Cytoskeleton:  Intermediate filaments; actin
Mar 18 Cytoskeleton: actin binding proteins; microtubules
Mar 25


Cytoskeleton: microtubules
April 1


Exam 3: in class Multiple choice questions (individual assignment)
Apr 8 Extracellular matrix; cell adhesion; coordinated polarization.
Apr  15 Cell motility and Wnt Signal Signaling. 
Apr  22 Medical consequences of aberrant signaling pathways; production of small molecules for protein kinases In cancer therapy.
Study days
May 6 Exam 4: In class presentation (group assignment)


Below is Powerpoint presentations for Lesson 1 and Lesson 2.  Please check for UPDATES on this page for additional supplemental information for these Lessons including articles from this Online Access Journal


cell signaling and motility 1 lesson


cell signaling and motility 2 lesson

The following articles and curations discuss about the new paradigm how we now envision DNA, in particular how we now understand that the important parts of the genome are not just the exons which code for proteins but also the intronic DNA, which contains all the regulatory elements such as promoters, lnDNA, miRNA sequences etc.  These are good reads for your presentations.

The Search for the Genetic Code

Junk DNA codes for valuable miRNAs


And on How the Cell Creates Diversity post the Genetic Code by Use of Post Translational Modifications to Bring Diversity to Protein Structure/Function

Expanding the Genetic Alphabet and Linking the Genome to the Metabolome

Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

Also there is a link to a Blood article using FISH to detect gene amplifications after Gleevec resistance onset here

Novel Mechanisms of Resistance to Novel Agents

Other Articles related to the #TUBiol3373 course include:

Lesson 9 Cell Signaling: Curations and Articles of reference as supplemental information for lecture section on WNTs: #TUBioll3373

Curation of selected topics and articles on Role of G-Protein Coupled Receptors in Chronic Disease as supplemental information for #TUBiol3373


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Curation of selected topics and articles on Role of G-Protein Coupled Receptors in Chronic Disease as supplemental information for #TUBiol3373

Curator: Stephen J. Williams, PhD 

Below is a series of posts and articles related to the role of G protein coupled receptors (GPCR) in various chronic diseases.  This is only a cursory collection and by no means represents the complete extensive literature on pathogenesis related to G protein function or alteration thereof.  However it is important to note that, although we think of G protein signaling as rather short lived, quick, their chronic activation may lead to progression of various disease. As to whether disease onset, via GPCR, is a result of sustained signal, loss of desensitization mechanisms, or alterations of transduction systems is an area to be investigated.


Molecular Pathogenesis of Progressive Lung Diseases

Author: Larry H. Bernstein, MD, FCAP


Chronic Obstructive Lung Disease (COPD)

Inflammatory and infectious factors are present in diseased airways that interact with G-protein coupled receptors (GPCRs), such as purinergic receptors and bradykinin (BK) receptors, to stimulate phospholipase C [PLC]. This is followed by the activation of inositol 1,4,5-trisphosphate (IP3)-dependent activation of IP3 channel receptors in the ER, which results in channel opening and release of stored Ca2+ into the cytoplasm. When ER Ca2+ stores are depleted a pathway for Ca2+ influx across the plasma membrane is activated. This has been referred to as “capacitative Ca2+ entry”, and “store-operated calcium entry” (3). In the next step PLC mediated Ca2+ i is mobilized as a result of GPCR activation by inflammatory mediators, which triggers cytokine production by Ca2+ i-dependent activation of the transcription factor nuclear factor kB (NF-kB) in airway epithelia.




In Alzheimer’s Disease

Important Lead in Alzheimer’s Disease Model

Larry H. Bernstein, MD, FCAP, Curator discusses findings from a research team at University of California at San Diego (UCSD) which the neuropeptide hormone corticotropin-releasing factor (CRF) as having an important role in the etiology of Alzheimer’s Disease (AD). CRF activates the CRF receptor (a G stimulatory receptor).  It was found inhibition of the CRF receptor prevented cognitive impairment in a mouse model of AD.  Furthermore researchers at the Flanders Interuniversity Institute for Biotechnology found the loss of a protein called G protein-coupled receptor 3 (GPR3) may lower the amyloid plaque aggregation, resulting in improved cognitive function.  Additionally inhibition of several G-protein coupled receptors alter amyloid precursor processing, providing a further mechanism of the role of GPCR in AD (see references in The role of G protein-coupled receptors in the pathology of Alzheimer’s disease by Amantha Thathiah and Bart De Strooper Nature Reviews Feb 2011; 12: 73-87 and read post).


In Cardiovascular and Thrombotic Disease


Adenosine Receptor Agonist Increases Plasma Homocysteine


and read related articles in curation on effects of hormones on the cardiovascular system at

Action of Hormones on the Circulation


In Cancer

A Curated History of the Science Behind the Ovarian Cancer β-Blocker Trial


Further curations and references of G proteins and chronic disease can be found at the Open Access journal using the search terms “GCPR” and “disease” in the Search box in the upper right of the home page.







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